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There are significant barriers in engaging pregnant and postpartum women that are considered high-risk (e.g., those experiencing substance use and/or substance use disorders (SUD)) into longitudinal research studies. To improve recruitment and retention of this population in studies spanning from the prenatal period to middle childhood, it is imperative to determine ways to improve key research engagement factors. The current manuscript uses a qualitative approach to determine important factors related to recruiting, enrolling, and retaining high-risk pregnant and postpartum women. The current sample included 41 high-risk women who participated in focus groups or individual interviews. All interviews were analyzed to identify broad themes related to engaging high-risk pregnant and parenting women in a 10-year longitudinal research project. Themes were organized into key engagement factors related to the following: (1) recruitment strategies, (2) enrollment, and (3) retention of high-risk pregnant and parenting women in longitudinal research studies. Results indicated recruitment strategies related to ideal recruitment locations, material, and who should share research study information with high-risk participants. Related to enrollment, key areas disclosed focused on enrollment decision-making, factors that create interest in joining a research project, and barriers to joining a longitudinal research study. With regard to retention, themes focused on supports needed to stay in research, barriers to staying in research, and best ways to stay in contact with high-risk participants. Overall, the current qualitative data provide preliminary data that enhance the understanding of a continuum of factors that impact engagement of high-risk pregnant and postpartum women in longitudinal research with current results indicating the need to prioritize recruitment, enrollment, and retention strategies in order to effectively engage vulnerable populations in research.

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Current efforts to design research on developmental effects of prenatal opioid exposure can benefit from knowledge gained from 50 years of studies of fetal alcohol and prenatal drug exposures such as cocaine. Scientific advances in neurobiology, developmental psychopathology, infant assessments, genetics, and imaging support the principles of developmental neurotoxicology that guide research in prenatal exposures. Important to research design is accurate assessment of amount, frequency, and timing of exposure which benefits from accurate self-report and biomarkers of exposure. Identifying and control of pre- and postnatal factors that impact development are difficult and dependent on appropriate research design and selection of comparison groups and measurement of confounding, mediating, and moderating variables. Polysubstance exposure has increased due to the number of prescribed and nonprescribed substances used by pregnant women and varying combinations of drugs may have differential effects on the outcome. Multiple experimental and clinical assessments of infant behavior have been developed but predicting outcome before 18-24 months of age remains difficult. With some exceptions, prenatal substance exposure effect sizes have been small, and cognitive and behavioral effects tend to be specific rather than global. Studies require large sample sizes, adequate retention, and support for social services in at-risk samples. The ethical and legal contexts and stigma associated with drug/alcohol use disorder should be considered in order to prevent harm to families in research programs. Recognition of the pervasive use of addictive substances in this nation should lead to broad scientific efforts to understand how substances affect child outcomes and to initiate prevention and intervention where needed.

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This manuscript is the result of an interdisciplinary team approach to examine the ethical and cultural considerations of biospecimen collection among American Indian and Alaskan Native (AIAN) communities for the planned Healthy Brain and Child Development (HBCD) study. We begin by reviewing a brief history of the treatment of AIAN communities by the US government and within research studies. Based in part on this history, we highlight the overlapping and intersecting vulnerabilities of AIAN communities, including historical trauma, poverty, lack of healthcare access, and environmental hazards. After consideration of ethical and legal implications, we introduce our recommendations for biospecimen collection/biobanking with AIAN communities in the context of population-representative, multi-site, national studies. We recommend the following key considerations: (1) authentic partnership development; (2) beneficence to the community; (3) culturally respectful research design; (4) meaningful consent to support enrollment and retention; (5) culturally appropriate data management. Adherence to a culturally aware approach for inclusion of underrepresented communities assures external validity in the national studies and increases likelihood of bidirectional value exchange.

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Defining reliable brain markers for the prediction of abnormal behavioral outcomes remains an urgent but extremely challenging task in neuroscience research. This is particularly important for infant studies given the most dramatic brain and behavioral growth during infancy.

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Prenatal drug exposure (PDE) is known to affect fetal brain development with documented long-term consequences. Most studies of PDE effects on the brain are based on animal models. In this study, based on a large sample of 133 human neonates and leveraging a novel linear mixed-effect model designed for intersubject variability analyses, we studied the effects of six prenatally exposed drugs (i.e., nicotine, alcohol, selective serotonin reuptake inhibitor, marijuana, cocaine, and opioids) on neonatal whole-brain functional organization and compared them with five other critical nondrug variables (i.e., gestational age at birth/scan, sex, birth weight, and maternal depression). The behavioral implications were also examined. Magnitude-wise, through summing across individual drug effects, our results highlighted ~5% of whole-brain functional connections (FCs) affected by PDE, which was highly comparable with the combined effects of the five nond rug variables. Spatially, the detected PDE effects featured drug-specific patterns with a common bias in higher-order brain regions/networks. Regarding brain-behavioral relationships, the detected connections showing significant drug effects also demonstrated significant correlations with 3-month behavioral outcomes. Further mediation analyses supported a mediation role of the detected brain FCs between PDE status and cognitive/language outcomes. Our findings of widespread, and spatially biased PDE effect patterns coupled with significant behavioral implications may hopefully stimulate more human-based studies into effects of PDE on long-term developmental outcomes.

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Prenatal development is a time when the brain is acutely vulnerable to insult and alteration by environmental factors (e.g., toxins, maternal health). One important risk factor is maternal obesity (Body Mass Index > 30). Recent research indicates that high maternal BMI during pregnancy is associated with increased risk for numerous physical health, cognitive, and mental health problems in offspring across the lifespan. It is possible that heightened maternal prenatal BMI influences the developing brain even before birth.

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Infants with prenatal substance exposure are at increased risk for developmental problems, with self-regulatory challenges being some of the most pronounced. The current study aimed to investigate the extent to which prenatal substance exposure (alcohol, opioids) impacts infant self-regulation during a relational stressor and the association between self-regulation and infant affect.

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To test the performance of the MPnRAGE motion-correction algorithm on quantitative relaxometry estimates.

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Two of the most commonly used substances by adolescents in the United States are cannabis and alcohol. Cannabis use disorder (CUD) and alcohol use disorder (AUD) are associated with impairments in decision-making processes. One mechanism for impaired decision-making in these individuals is thought to be an inability to adequately represent future events during decision-making. In the current study involving 112 adolescents, we used a comparative optimism task to examine the relationship between relative severity of CUD/AUD (as indexed by the CUD/AUD Identification Tests [CUDIT/AUDIT]) and atypical function within neural systems underlying affect-based neural represenation future events. Greater CUDIT scores were negatively related to responses within subgenual anterior and posterior cingulate cortex when processing high-intensity potential future positive and negative events. There was also a particularly marked negative relationship between CUD symptoms and blood oxygen level-dependent (BOLD) responses within visual and premotor cortices to high-intensity, negatively valenced potential future events. However, AUD symptom severity was not associated with dysfunction within these brain regions. These data indicate that relative risk/severity of CUD is associated with reduced responsiveness to future high-intensity events. This may impair decision-making where future significant consequences should guide response choice.

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The two most commonly used illegal substances by adolescents in the United States are alcohol and cannabis. Alcohol use disorder (AUD) and cannabis use disorder (CUD) have been associated with dysfunction in decision-making processes in adolescents. One potential mechanism for these impairments is thought to be related to abnormalities in reward and punishment processing. However, very little work has directly examined potential differential relationships between AUD and CUD symptom severity and neural dysfunction during decision making in adolescents.

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Magnetic resonance imaging, histological, and gene analysis approaches in living and nonliving human fetuses and in prematurely born neonates have provided insight into the staged processes of prenatal brain development. Increased understanding of micro- and macroscale brain network development before birth has spurred interest in understanding the relevance of prenatal brain development to common neurological diseases. Questions abound as to the sensitivity of the intrauterine brain to environmental programming, to windows of plasticity, and to the prenatal origin of disorders of childhood that involve disruptions in large-scale network connectivity. Much of the available literature on human prenatal neural development comes from cross-sectional or case studies that are not able to resolve the longitudinal consequences of individual variation in brain development before birth. This review will 1) detail specific methodologies for studying the human prenatal brain, 2) summarize large-scale human prenatal neural network development, integrating findings from across a variety of experimental approaches, 3) explore the plasticity of the early developing brain as well as potential sex differences in prenatal susceptibility, and 4) evaluate opportunities to link specific prenatal brain developmental processes to the forms of aberrant neural connectivity that underlie common neurological disorders of childhood.

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Magnetic resonance imaging, histological, and gene analysis approaches in living and nonliving human fetuses and in prematurely born neonates have provided insight into the staged processes of prenatal brain development. Increased understanding of micro- and macroscale brain network development before birth has spurred interest in understanding the relevance of prenatal brain development to common neurological diseases. Questions abound as to the sensitivity of the intrauterine brain to environmental programming, to windows of plasticity, and to the prenatal origin of disorders of childhood that involve disruptions in large-scale network connectivity. Much of the available literature on human prenatal neural development comes from cross-sectional or case studies that are not able to resolve the longitudinal consequences of individual variation in brain development before birth. This review will 1) detail specific methodologies for studying the human prenatal brain, 2) summarize large-scale human prenatal neural network development, integrating findings from across a variety of experimental approaches, 3) explore the plasticity of the early developing brain as well as potential sex differences in prenatal susceptibility, and 4) evaluate opportunities to link specific prenatal brain developmental processes to the forms of aberrant neural connectivity that underlie common neurological disorders of childhood.

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This review examines how research focused on treatment for opioid use in perinatal populations and preventive interventions for postpartum psychopathology have remained separate, despite significant overlap.

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Test-retest of automated image segmentation algorithms (FSL FAST, FSL FIRST, and FREESURFER) are computed on magnetic resonance images from 12 unsedated children aged 9.4±2.6 years ([min,max] ​= ​[6.5 years, 13.8 years]) using different approaches to motion correction (prospective versus retrospective). The prospective technique, PROMO MPRAGE, dynamically estimates motion using specially acquired navigator images and adjusts the remaining acquisition accordingly, whereas the retrospective technique, MPnRAGE, uses a self-navigation property to retrospectively estimate and account for motion during image reconstruction. To increase the likelihood and range of motions, participants heads were not stabilized with padding during repeated scans. When motion was negligible both techniques had similar performance. When motion was not negligible, the automated image segmentation and anatomical labeling software tools showed the most consistent performance with the retrospectively corrected MPnRAGE technique (≥80% volume overlaps for 15 of 16 regions for FIRST and FREESURFER, with greater than 90% volume overlaps for 12 regions with FIRST and 11 regions with FREESURFER). Prospectively corrected MPRAGE with linear view-ordering also demonstrated lower performance than MPnRAGE without retrospective motion correction.

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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. 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 Understanding the developmental trajectory of brain connectivity provides a basis for understanding how the prenatal period shapes future brain function and disease dysfunction.

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This study describes maternal and infant contributions to dyadic affective exchanges during the Still-Face Paradigm (SFP) in an understudied mostly low-income sample. One hundred eleven mothers and their 7-month-old infants were videotaped during the SFP to analyze how a social stressor affects mother-infant positive and negative affective exchanges during interaction. The SFP includes 3 episodes: baseline, maternal still-face, and reunion. Maternal and infant positive and negative affect were scored by masked reliable coders. Data were analyzed using the Actor-Partner Interdependence Model to test the hypotheses that each partner’s affectivity during the baseline episode would predict their own affectivity during the reunion episode (actor effects). We also expected that each partner’s affectivity during the baseline episode would influence the other partner’s affectivity during the reunion episodes (partner effects). After controlling for infant sex and maternal education, results provided evidence for actor effects for maternal and infant positive affect, and for partner effects for maternal baseline positive affect to infant positive affect during the reunion. One significant partner effect was observed for negative affect: Infant negativity during baseline predicted greater maternal negativity during reunion. Findings confirm that both mothers and infants contribute to dyadic affective processes during the SFP but specific findings vary depending on the affective valence in question. Clinical implications and future research are discussed.

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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.

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The developmental impact of opioid use during pregnancy is a subject of ongoing debate. Short-term neonatal outcomes, such as lower birth weight and neonatal abstinence syndrome, are the most well-recognized outcomes. However, knowledge gaps exist regarding longer-term neurocognitive and mental health outcomes. In this article, we summarize an expert panel discussion that was held in April 2018 by the Substance Abuse and Mental Health Services Administration and attended by national experts in the field of perinatal opioid exposure and its impact on child development. Despite the challenges with research in this area, there is emerging literature revealing an association between neonates exposed to opioids in utero and longer-term adverse neurocognitive, behavioral, and developmental outcomes. Although adverse sequalae may not be apparent in the neonatal period, they may become more salient as children develop and reach preschool and school age. Multiple variables (genetic, environmental, and biological) result in a highly complex picture. The next steps and strategies to support families impacted by opioid use disorder are explored. Model programs are also considered, including integrated care for the child and mother, parenting supports, and augmentations to home visiting.

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Despite the proliferation of fentanyl and fentanyl-adulterated opioids in North America, the impacts of this drug market change on injection initiation processes have not been examined. With the aim of informing structural interventions to address injection initiation and related harms, we explore how people who inject drugs (PWID) in Vancouver, Canada understand and navigate social norms of initiating others into injecting within the context of an overdose crisis. In-depth qualitative interviews were conducted with 19 PWID who reported helping someone inject for the first time. Participants were recruited from two cohort studies of PWID. Participants articulated moral dilemmas about assisting others with injecting. While participants described a ‘moral code’ prohibiting assisting injection-naïve individuals, this code was not the sole consideration shaping social action around injection initiation. Rather, PWID exercised agency about whether and how to assist novice injectors within the context of constraining and enabling social norms around practicing interpersonal responsibility. Changes to the drug market heightened feelings of moral culpability and criminal liability among PWID who assisted others into injection, given that injecting heightened initiates’ risk of overdose. These concerns operated in tension with the aim of protecting novice injectors from harms associated with an increasingly potent and unpredictable drug supply by providing them with injection assistance, education and supervision. Our analysis of how PWID practice interpersonal responsibility helps conceptualise how ‘moral codes’ prohibiting initiation assistance are managed and negotiated amidst structural vulnerability. Structural interventions reducing the vulnerability of novice injectors should be prioritized, including the implementation of supervised injection sites allowing for assisted injection, Good Samaritan laws, and policy changes conducive to a safer drug supply.

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Sex-related differences in brain and behavior are apparent across the life course, but the exact set of processes that guide their emergence in utero remains a topic of vigorous scientific inquiry. Here, we evaluate sex and gestational age (GA)-related change in functional connectivity (FC) within and between brain wide networks. Using resting-state functional magnetic resonance imaging we examined FC in 118 human fetuses between 25.9 and 39.6 weeks GA (70 male; 48 female). Infomap was applied to the functional connectome to identify discrete prenatal brain networks in utero. A consensus procedure produced an optimal model comprised of 16 distinct fetal neural networks distributed throughout the cortex and subcortical regions. We used enrichment analysis to assess network-level clustering of strong FC-GA correlations separately in each sex group, and to identify network pairs exhibiting distinct patterns of GA-related change in FC between males and females. We discovered both within and between network FC-GA associations that varied with sex. Specifically, associations between GA and posterior cingulate-temporal pole and fronto-cerebellar FC were observed in females only, whereas the association between GA and increased intracerebellar FC was stronger in males. These observations confirm that sexual dimorphism in functional brain systems emerges during human gestation.

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The adult human brain is organized into functional brain networks, groups of functionally connected segregated brain regions. A key feature of adult functional networks is long-range selectivity, the property that spatially distant regions from the same network have higher functional connectivity than spatially distant regions from different networks. Although it is critical to establish the status of functional networks and long-range selectivity during the neonatal period as a foundation for typical and atypical brain development, prior work in this area has been mixed. Although some studies report distributed adult-like networks, other studies suggest that neonatal networks are immature and consist primarily of spatially isolated regions. Using a large sample of neonates (n = 262), we demonstrate that neonates have long-range selective functional connections for the default mode, fronto-parietal, and dorsal attention networks. An adult-like pattern of functional brain networks is evident in neonates when network-detection algorithms are tuned to these long-range connections, when using surface-based registration (versus volume-based registration), and as per-subject data quantity increases. These results help clarify factors that have led to prior mixed results, establish that key adult-like functional network features are evident in neonates, and provide a foundation for studies of typical and atypical brain development.

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