Faculty Bibliography

In response to the COVID-19 pandemic, research institutions across the globe have modified their operations in ways that have limited or eliminated the amount of permissible in-person research interaction. In order to prevent the loss of important developmentally-timed data during the pandemic, researchers have quickly pivoted and developed innovative methods for remote assessment of research participants. In this manuscript, we describe methods developed for remote assessment of a parent child cohort with a focus on examining the perinatal environment, behavioral and biological indicators of child neurobehavioral development, parent-child interaction, as well as parent and child mental and physical health. We include recommendations relevant to adapting in-laboratory assessments for remote data collection and conclude with a description of the successful dissemination of the methods to eight research sites across the United States, each of whom are involved in Phase 1 of the HEALthy Brain and Child Development (HBCD) Study. These remote methods were born out of pandemic-related necessity; however, they have much wider applicability and may offer advantages over in-laboratory neurodevelopmental assessments.

OBJECTIVE:Our objectives were to assess in perinatal women: the most effective methods used to meet social support needs during COVID-19, the impact of COVID-19 on self-reported social support levels, and how perceived change in social support related to distress, depression, and mental health. DESIGN/METHODS:One-time survey administered from April to August 2020 SETTING: Online PARTICIPANTS: Pregnant and postpartum women with infants less than 6 months of age MEASUREMENT AND FINDINGS: Participants indicated the methods they used to meet social support needs during COVID-19. They self-rated their social support level pre- and during pandemic and their distress, depressive symptoms, and mental health changes on a Likert scale. Out of 1142 participants, the most effective methods for obtaining social support during the pandemic were virtual means (e.g. video call) and interaction with friends. There was a significant difference in distribution of self-reported levels of social support before and during the pandemic, with more respondents reporting a decrease in support. Decreases in social support were associated with higher distress levels, higher levels of depressive symptoms, and poorer mental health. KEY CONCLUSIONS/CONCLUSIONS:Perinatal women reported decreased social support during the COVID-19 pandemic which was associated with poorer mental health. Using virtual means of social support and support provided by friends had the largest positive effect on perceived social support levels. IMPLICATIONS FOR PRACTICE/CONCLUSIONS:Interventions using virtual support means from friends may be helpful to improve social support and mental health in this population.

A major challenge in designing large-scale, multi-site studies is developing a core, scalable protocol that retains the innovation of scientific advances while also lending itself to the variability in experience and resources across sites. In the development of a common Healthy Brain and Child Development (HBCD) protocol, one of the chief questions is "is fetal MRI ready for prime-time?" While there is agreement about the value of prenatal data obtained non-invasively through MRI, questions about practicality abound. There has been rapid progress over the past years in fetal and placental MRI methodology but there is uncertainty about whether the gains afforded outweigh the challenges in supporting fetal MRI protocols at scale. Here, we will define challenges inherent in building a common protocol across sites with variable expertise and will propose a tentative framework for evaluation of design decisions. We will compare and contrast various design considerations for both normative and high-risk populations, in the setting of the post-COVID era. We will conclude with articulation of the benefits of overcoming these challenges and would lend to the primary questions articulated in the HBCD initiative.

Increasing evidence supports a link between maternal prenatal cannabis use and altered neural and physiological development of the child. However, whether cannabis use relates to altered human brain development prior to birth, and specifically, whether maternal prenatal cannabis use relates to connectivity of fetal functional brain systems, remains an open question. The major objective of this study was to identify whether maternal prenatal cannabis exposure (PCE) is associated with variation in human brain hippocampal functional connectivity prior to birth. Prenatal drug toxicology and fetal fMRI data were available in a sample of 115 fetuses [43 % female; mean age 32.2 weeks (SD = 4.3)]. Voxelwise hippocampal connectivity analysis in a subset of age and sex-matched fetuses revealed that PCE was associated with alterations in fetal dorsolateral, medial and superior frontal, insula, anterior temporal, and posterior cingulate connectivity. Classification of group differences by age 5 outcomes suggest that compared to the non-PCE group, the PCE group is more likely to have increased connectivity to regions associated with less favorable outcomes and to have decreased connectivity to regions associated with more favorable outcomes. This is preliminary evidence that altered fetal neural connectome may contribute to neurobehavioral vulnerability observed in children exposed to cannabis in utero.

PURPOSE/OBJECTIVE:The National Institutes of Health announced the Healthy Brain and Child Development (HBCD) study to further understanding of infant brain development. This study examined perceptions and knowledge about research among the demographic groups to be studied in HBCD. METHOD/METHODS:1164 participants (n = 548 pregnant people and 616 mothers of infants < 12 months) completed anonymous, on-line surveys. Domains included research literacy, MRI knowledge, and attitudes about research incentives and biospecimen collection. Logistic regression was used to examine factors related to outcome variables. RESULTS:Knowledge of MRI safety was low and research literacy was high across participants. Likelihood of participation given various incentives differed between participants. Those with lower education were less likely to rate any items as increasing likelihood of participation. Substance use during pregnancy improved the model fit only for items about alternate visit structures (home and telephone visits) and confidentiality. CONCLUSION/CONCLUSIONS:Overall results support the feasibility of infant imaging studies, such as HBCD with respondents having high research literacy and interest in learning about their baby's development. Educating potential participants about MRI safety and providing flexible incentives for participation will improve the success of infant MRI studies.

BACKGROUND:Increasing reports of long-term symptoms following COVID-19 infection, even among mild cases, necessitates systematic investigation into the prevalence and type of lasting illness. Notably, there is limited data regarding the influence of social determinants of health, like perceived discrimination and economic stress, which may exacerbate COVID-19 health risks. The primary goals of this study are to test the bearing of subjective experiences of discrimination, financial security, and quality of care on illness severity and lasting symptom complaints. METHODS:logistic regressions tested social determinants hypothesized to predict neurological, cognitive, or mood symptoms. RESULTS:70.6% of patients reported presence of one or more lasting symptoms after recovery. Neural systems were especially impacted, and 19.4% and 25.1% of patients reported mood or cognitive/memory complaints, respectively. Path models demonstrated that frequency and stress about experiences of discrimination predicted increased illness severity and increased lasting symptom count, even when adjusting for sociodemographic factors and mental/physical health comorbidities. Notably, this effect was specific to stress related to discrimination, and did not extend to general stress levels. Further, perceived but not objective socioeconomic status (SES) was associated with increased lasting symptom complaints after recovery. Finally, associations between discrimination and illness differed with individual perceptions about quality of medical care. CONCLUSIONS:Lasting symptoms after recovery from COVID-19 are highly prevalent and neural systems are significantly impacted. Importantly, psychosocial factors (perceived discrimination and perceived SES) can exacerbate individual health risk. This study provides actionable directions for improved health outcomes by establishing that sociodemographic risk and medical care influence near and long-ranging health outcomes.

Studies reporting significant associations between maternal prenatal stress and child outcomes are frequently confounded by correlates of prenatal stress that influence the postnatal rearing environment. The major objective of this study is to identify whether maternal prenatal stress is associated with variation in human brain functional connectivity prior to birth. We utilized fetal fMRI in 118 fetuses [48 female; mean age 32.9 weeks (SD = 3.87)] to evaluate this association and further addressed whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Community detection was used to empirically define networks and enrichment was used to isolate differential within- or between-network connectivity effects. Significance for χ² enrichment was determined by randomly permuting the subject pairing of fetal brain connectivity and maternal stress values 10,000 times. Mixtures modelling was used to test whether fetal neural differences were related to maternal health behaviors, social support, or birth outcomes. Increased maternal prenatal negative affect/stress was associated with alterations in fetal frontoparietal, striatal, and temporoparietal connectivity (β = 0.82, p < 0.001). Follow-up analysis demonstrated that these associations were stronger in women with better health behaviors, more positive interpersonal support, and lower overall stress (β = 0.16, p = 0.02). Additionally, magnitude of stress-related differences in neural connectivity was marginally correlated with younger gestational age at delivery (β = -0.18, p = 0.05). This is the first evidence that negative affect/stress during pregnancy is reflected in functional network differences in the human brain in utero, and also provides information about how positive interpersonal and health behaviors could mitigate prenatal brain programming.

First-person accounts of COVID-19 illness and treatment complement and enrich data derived from electronic medical or public health records. With patient-reported data, it is uniquely possible to ascertain in-depth contextual information as well as behavioral and emotional responses to illness. The Novel Coronavirus Illness Patient Report (NCIPR) dataset includes complete survey responses from 1,592 confirmed COVID-19 patients ages 18 to 98. NCIPR survey questions address symptoms, medical complications, home and hospital treatments, lasting effects, anxiety about illness, employment impacts, quarantine behaviors, vaccine-related behaviors and effects, and illness of other family/household members. Additional questions address financial security, perceived discrimination, pandemic impacts (relationship, social, stress, sleep), health history, and coping strategies. Detailed patient reports of illness, environment, and psychosocial impact, proximal to timing of infection and considerate of demographic variation, is meaningful for understanding pandemic-related public health from the perspective of those that contracted the disease.

Background: Autism spectrum disorder (ASD) is a highly prevalent developmental disorder. There is notable disparity in occurrence rates between males and females, with males being 4.5 times as likely as their female counterparts to be diagnosed with the disease. A major objective for improving functional outcomes in ASD is to isolate biomarkers for earlier detection; an area as yet unexplored is whether biomarkers of future ASD symptomology may be observable in the fetal brain. Here, we focus on the amygdala, which shows sex-differential patterns of development and has been implicated in the neurobiology of ASD.
Method(s): We obtained resting-state MRI data in 109 healthy human fetuses (24-39 weeks) and Brief Infant Toddler Social Emotional Assessment (BITSEA) and Child Behavior Checklist (CBCL) measures at child age 3. The average number of frames obtained after scrubbing high-motion frames was N=169, or 5.6 minutes of resting state data (TR=2) with mean XYZ motion 0.9mm (SD=0.3). Subject-specific amygdala connectivity maps were computed and tested in a full factorial model, that included sex, age at scan, and ASD outcome.
Result(s): ASD outcomes were associated with increased amygdala connectivity to prefrontal and sensorimotor cortices, decreased connectivity to anterior insula and cerebellum, and sex interactions were observed in inferior prefrontal and striatal regions (p<0.005 and k min=25).
Conclusion(s): These observations raise exciting new ideas about the advent of risk and the ontogeny of early sex differences. Further analyses will be conducted to examine sex-differential risk and postnatal environmental effects within a multifactorial liability model framework. Supported By: NIMH R01 MH110793 NIDA R34 DA050287 NIMH R01 MH122447 NARSAD Foundation Keywords: Fetal, Autism, Resting-State, Sex Differences
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