Network localization of pediatric lesion-induced dystonia.

Objective: Dystonia is a movement disorder defined by involuntary muscle contractions leading to abnormal postures or twisting and repetitive movements. Classically dystonia has been thought of as a disorder of the basal ganglia, but newer results in idiopathic dystonia and lesion-induced dystonia in adults point to broader motor network dysfunction spanning the basal ganglia, cerebellum, premotor cortex, sensorimotor, and frontoparietal regions. It is unclear whether a similar network is shared between different etiologies of pediatric lesion-induced dystonia. Methods: Three cohorts of pediatric patients with lesion-induced dystonia were identified. The lesion etiologies included hypoxia, kernicterus, and stroke versus comparison subjects with acquired lesions not associated with dystonia. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with dystonia. Results: Multivariate lesion-symptom mapping showed that lesions of the putamen (stroke: r = 0.50, p <0.01; hypoxia, r = 0.64, p <0.001) and globus pallidus (kernicterus, r = 0.61, p <0.01) were associated with dystonia. Lesion network mapping using normative connectome data from healthy children demonstrated that these regional findings occurred within a common brain-wide network that involves the basal ganglia, anterior and medial cerebellum, and cortical regions that overlap the cingulo-opercular and somato-cognitive-action networks. Interpretation: We interpret these findings as novel evidence for a unified dystonia brain network that involves the somato-cognitive-action network, which is involved in higher order coordination of movement. Elucidation of this network gives insight into the functional origins of dystonia and provides novel targets to investigate for therapeutic intervention.

Characteristics of women concordant and discordant for urine drug screens for cannabis exposure and self-reported cannabis use during pregnancy.

BACKGROUND: Increasing cannabis use among pregnant people and equivocal evidence linking prenatal cannabis exposure to adverse outcomes in offspring highlights the need to understand its potential impact on pregnancy and child outcomes. Assessing cannabis use during pregnancy remains a major challenge with potential influences of stigma on self-report as well as detection limitations of easily collected biological matrices. OBJECTIVE: This descriptive study examined the concordance between self-reported (SR) cannabis use and urine drug screen (UDS) detection of cannabis exposure during the first trimester of pregnancy and characterized concordant and discordant groups for sociodemographic factors, modes of use, secondhand exposure to cannabis and tobacco, and alcohol use and cotinine positivity. STUDY DESIGN: The Cannabis Use During Development and Early Life (CUDDEL) Study is an ongoing longitudinal study that recruits pregnant individuals presenting for obstetric care, who report lifetime cannabis use as well as using (n = 289) or not using cannabis (n = 169) during pregnancy. During the first trimester pregnancy visit, SR of cannabis use and a UDS for cannabis, other illicit drugs and nicotine are acquired from eligible participants, of whom 333 as of 05/01/2023 had both. RESULTS: Using available CUDDEL Study data on both SR and UDS (n = 333; age 26.6 ± 4.7; 88.6% Black; 45.4% below federal poverty threshold; 56.5% with paid employment; 89% with high school education; 22% first pregnancy; 12.3 ± 3.6 weeks gestation), we classified pregnant individuals with SR and UDS data into 4 groups based on concordance (k = 0.49 [95% C.I. 0.40-0.58]) between SR cannabis use and UDS cannabis detection during the first trimester: 1) SR+/UDS+ (n = 107); 2) SR-/UDS- (n = 142); 3) SR+/UDS- (n = 44); 4) SR-/UDS+ (n = 40). Those who were SR+/UDS- reported less frequent cannabis use and fewer hours under the influence of cannabis during their pregnancy. Those who were SR-/UDS+ were more likely to have joined the study at a lower gestational age with 62.5% reporting cannabis use during their pregnancy prior to being aware that they were pregnant. Of the 40 SR-/UDS+ women, 14 (i.e., 35%) reported past month secondhand exposure, or blunt usage. In the subset of individuals with SR and UDS available at trimester 2 (N = 160) and 3 (N = 140), concordant groups were mostly stable and > 50% of those in the discordant groups became concordant by the second trimester. Classifying individuals as exposed or not exposed who were SR+ and/or UDS+ resulted in minor changes in group status based on self-report at screening. CONCLUSION: Overall, there was moderate concordance between SR and UDS for cannabis use/exposure during pregnancy. Instances of SR+/UDS- discordancy may partially be attributable to lower levels of use that are not detected on UDS. SR-/UDS+ discordancy may arise from recent use prior to knowledge of pregnancy, extreme secondhand exposure, deception, and challenges with completing questionnaires. Acquiring both self-report and biological detection of cannabis use/exposure allows for the examination of convergent evidence. Classifying those who are SR+ and/or UDS+ as individuals who used cannabis during their first trimester after being aware of their pregnancy resulted in only a minor change in exposure status; thus, relying on self-report screening, at least in this population and within this sociocultural context likely provides an adequate approximation of cannabis use during pregnancy.

Basic Environmental Supports for Positive Brain and Cognitive Development in the First Year of Life.

Importance: Defining basic psychosocial resources to facilitate thriving in the first year of life could tangibly inform policy and enhance child development worldwide. Objective: To determine if key environmental supports measured as a thrive factor (T-factor) in the first year of life positively impact brain, cognitive, and socioemotional outcomes through age 3. Design, Setting, and Participants: This prospective longitudinal cohort study took place at a Midwestern academic medical center from 2017 through 2022. Participants included singleton offspring oversampled for those facing poverty, without birth complications, congenital anomalies, or in utero substance exposures (except cigarettes and marijuana) ascertained prenatally and followed up prospectively for the first 3 years of life. Data were analyzed from March 9, 2023, through January 3, 2024. Exposures: Varying levels of prenatal social disadvantage advantage and a T-factor composed of environmental stimulation, nutrition, neighborhood safety, positive caregiving, and child sleep. Main outcomes & measures: Gray and white matter brain volumes and cortical folding at ages 2 and 3 years, cognitive and language abilities at age 3 years measured by the Bayley-III, and internalizing and externalizing symptoms at age 2 years measured by the Infant-Toddler Social and Emotional Assessment. Results: The T-factor was positively associated with child cognitive abilities (ß = 0.33; 95% CI, 0.14-0.52), controlling key variables including prenatal social disadvantage (PSD) and maternal cognitive abilities. The T-factor was associated with child language (ß = 0.36; 95% CI, 0.24-0.49), but not after covarying for PSD. The association of the T-factor with child cognitive and language abilities was moderated by PSD (ß = -0.32; 95% CI, -0.48 to -0.15 and ß = -0.36; 95% CI, -0.52 to -0.20, respectively). Increases in the T-factor were positively associated with these outcomes, but only for children at the mean and 1 SD below the mean of PSD. The T-factor was negatively associated with child externalizing and internalizing symptoms over and above PSD and other covariates (ß = -0.30; 95% CI, -0.52 to -0.08 and ß = -0.32; 95% CI, -0.55 to -0.09, respectively). Increasing T-factor scores were associated with decreases in internalizing symptoms, but only for children with PSD 1 SD above the mean. The T-factor was positively associated with child cortical gray matter above PSD and other covariates (ß = 0.29; 95% CI, 0.04-0.54), with no interaction between PSD and T-factor. Conclusions and Relevance: Findings from this study suggest that key aspects of the psychosocial environment in the first year impact critical developmental outcomes including cognitive, brain, and socioemotional development at age 3 years. This suggests that environmental resources and enhancement in the first year of life may facilitate every infant's ability to thrive, setting the stage for a more positive developmental trajectory.

Prenatal exposure to maternal disadvantage-related inflammatory biomarkers: associations with neonatal white matter microstructure.

Prenatal exposure to heightened maternal inflammation has been associated with adverse neurodevelopmental outcomes, including atypical brain maturation and psychiatric illness. In mothers experiencing socioeconomic disadvantage, immune activation can be a product of the chronic stress inherent to such environmental hardship. While growing preclinical and clinical evidence has shown links between altered neonatal brain development and increased inflammatory states in utero, the potential mechanism by which socioeconomic disadvantage differentially impacts neural-immune crosstalk remains unclear. In the current study, we investigated associations between socioeconomic disadvantage, gestational inflammation, and neonatal white matter microstructure in 320 mother-infant dyads over-sampled for poverty. We analyzed maternal serum levels of four cytokines (IL-6, IL-8, IL-10, TNF-α) over the course of pregnancy in relation to offspring white matter microstructure and socioeconomic disadvantage. Higher average maternal IL-6 was associated with very low socioeconomic status (SES; INR < 200% poverty line) and lower neonatal corticospinal fractional anisotropy (FA) and lower uncinate axial diffusivity (AD). No other cytokine was associated with SES. Higher average maternal IL-10 was associated with lower FA and higher radial diffusivity (RD) in corpus callosum and corticospinal tracts, higher optic radiation RD, lower uncinate AD, and lower FA in inferior fronto-occipital fasciculus and anterior limb of internal capsule tracts. SES moderated the relationship between average maternal TNF-α levels during gestation and neonatal white matter diffusivity. When these interactions were decomposed, the patterns indicated that this association was significant and positive among very low SES neonates, whereby TNF-α was inversely and significantly associated with inferior cingulum AD. By contrast, among the more advantaged neonates (lower-to-higher SES [INR ≥ 200% poverty line]), TNF-α was positively and significantly associated with superior cingulum AD. Taken together, these findings suggest that the relationship between prenatal cytokine exposure and white matter microstructure differs as a function of SES. These patterns are consistent with a scenario where gestational inflammation's effects on white matter development diverge depending on the availability of foundational resources in utero.

Disentangling Socioeconomic Status and Race in Infant Brain, Birth Weight, and Gestational Age at Birth: A Neural Network Analysis.

Background: Race is commonly used as a proxy for multiple features including socioeconomic status. It is critical to dissociate these factors, to identify mechanisms that affect infant outcomes, such as birth weight, gestational age, and brain development, and to direct appropriate interventions and shape public policy. Methods: Demographic, socioeconomic, and clinical variables were used to model infant outcomes. There were 351 participants included in the analysis for birth weight and gestational age. For the analysis using brain volumes, 280 participants were included after removing participants with missing magnetic resonance imaging scans and those matching our exclusion criteria. We modeled these three different infant outcomes, including infant brain, birth weight, and gestational age, with both linear and nonlinear models. Results: Nonlinear models were better predictors of infant birth weight than linear models (R2 = 0.172 vs. R2 = 0.145, p = .005). In contrast to linear models, nonlinear models ranked income, neighborhood disadvantage, and experiences of discrimination higher in importance than race while modeling birth weight. Race was not an important predictor for either gestational age or structural brain volumes. Conclusions: Consistent with the extant social science literature, the findings related to birth weight suggest that race is a linear proxy for nonlinear factors related to structural racism. Methods that can disentangle factors often correlated with race are important for policy in that they may better identify and rank the modifiable factors that influence outcomes.

Pro-inflammatory cerebrospinal fluid profile of neonates with intraventricular hemorrhage: clinical relevance and contrast with CNS infection.

BACKGROUND: Interpretation of cerebrospinal fluid (CSF) studies can be challenging in preterm infants. We hypothesized that intraventricular hemorrhage (IVH), post-hemorrhagic hydrocephalus (PHH), and infection (meningitis) promote pro-inflammatory CSF conditions reflected in CSF parameters. METHODS: Biochemical and cytological profiles of lumbar CSF and peripheral blood samples were analyzed for 81 control, 29 IVH grade 1/2 (IVH1/2), 13 IVH grade 3/4 (IVH3/4), 15 PHH, 20 culture-confirmed bacterial meningitis (BM), and 27 viral meningitis (VM) infants at 36.5 ± 4 weeks estimated gestational age. RESULTS: PHH infants had higher (p < 0.02) CSF total cell and red blood cell (RBC) counts compared to control, IVH1/2, BM, and VM infants. No differences in white blood cell (WBC) count were found between IVH3/4, PHH, BM, and VM infants. CSF neutrophil counts increased (p ≤ 0.03) for all groups compared to controls except IVH1/2. CSF protein levels were higher (p ≤ 0.02) and CSF glucose levels were lower (p ≤ 0.003) for PHH infants compared to all other groups. In peripheral blood, PHH infants had higher (p ≤ 0.001) WBC counts and lower (p ≤ 0.03) hemoglobin and hematocrit than all groups except for IVH3/4. CONCLUSIONS: Similarities in CSF parameters may reflect common pathological processes in the inflammatory response and show the complexity associated with interpreting CSF profiles, especially in PHH and meningitis/ventriculitis.

Maternal prenatal social disadvantage and neonatal functional connectivity: Associations with psychopathology symptoms at age 12 months.

Recent research has reported effects of socioeconomic status on neurobehavioral development as early as infancy, including positive associations between income and brain structure, functional connectivity, and behavior later in childhood (Ramphal, Whalen, et al., 2020; Triplett et al., 2022). This study extends this literature by investigating the relation of maternal prenatal social disadvantage (PSD) to neonatal amygdala and hippocampus functional connectivity and whether socioeconomic-related alterations in functional connectivity subsequently predict behavior at age 12 months in a large, socioeconomically diverse sample (N = 261 mother-infant dyads). PSD was assessed across gestation; neonatal magnetic resonance imaging was completed within the first weeks of life; and infant internalizing and externalizing symptoms were evaluated using the Infant-Toddler Social and Emotional Assessment at age 12 months. The results showed that PSD was significantly related to neonatal right amygdala and left hippocampus functional connectivity with prefrontal and motor-related regions. Social disadvantage-related right amygdala and left hippocampus functional connectivity with these regions was subsequently related to infant externalizing and internalizing symptoms at age 12 months. Building off an emerging literature exploring prenatal impacts on neonatal functional connectivity, this study further emphasizes the important role of the maternal environment during gestation on infant brain function and its relationship with externalizing and internalizing behavior in the first years of life. The results suggest that the prenatal socioeconomic environment may be a promising target for interventions aimed at improving infant neurobehavioral outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Functional parcellation of the neonatal cortical surface.

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that existing parcellations, including surface-based parcels derived from older samples as well as volume-based neonatal parcels, are a poor fit for neonatal surface data. We next derive a set of 283 cortical surface parcels from a sample of n = 261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.

Newborn Brain Function and Early Emerging Callous-Unemotional Traits.

Importance: Children with high callous-unemotional traits are more likely to develop severe and persistent conduct problems; however, the newborn neurobiology underlying early callous-unemotional traits remains unknown. Understanding the neural mechanisms that precede the development of callous-unemotional traits could help identify at-risk children and encourage development of novel treatments. Objective: To determine whether newborn brain function is associated with early-emerging empathy, prosociality, and callous-unemotional traits. Design, Setting, and Participants: In this prospective, longitudinal cohort study, pregnant women were recruited from obstetric clinics in St Louis, Missouri, from September 1, 2017, to February 28, 2020, with longitudinal data collected until March 20, 2023. Mothers were recruited during pregnancy. Newborns underwent brain magnetic resonance imaging shortly after birth. Mothers completed longitudinal follow-up when the children were aged 1, 2, and 3 years. Exposures: The sample was enriched for exposure to socioeconomic disadvantage. Main Outcome and Measure: Functional connectivity between hypothesized brain regions was assessed using newborn-specific networks and voxel-based connectivity analyses. Children's callous-unemotional traits were measured using the Inventory of Callous-Unemotional Traits. Empathy and prosociality were assessed using the Infant and Toddler Socio-Emotional Assessment. Results: A total of 283 children (mean [SD] gestational age, 38 [2] weeks; 159 male [56.2%]; 2 Asian [0.7%], 171 Black [60%], 7 Hispanic or Latino [2.5%], 106 White [38%], 4 other racial or ethnic group [1.4%]) were included in the analysis. Stronger newborn functional connectivity between the cingulo-opercular network (CO) and medial prefrontal cortex (mPFC) was associated with higher callous-unemotional traits at age 3 years (ß = 0.31; 95% CI, 0.17-0.41; P < .001). Results persisted when accounting for parental callous-unemotional traits and child externalizing symptoms. Stronger newborn CO-mPFC connectivity was also associated with lower empathy and lower prosociality at ages 1, 2, and 3 years using multilevel models (ß = -0.12; 95% CI, -0.21 to -0.04; P = .004 and ß = -0.20; 95% CI, -0.30 to -0.10; P < .001, respectively). Conclusions and Relevance: Newborn functional connectivity was associated with early-emerging empathy, prosociality, and callous-unemotional traits, even when accounting for parental callous-unemotional traits and child externalizing symptoms. Understanding the neurobiological underpinnings of empathy, prosociality, and callous-unemotional traits at the earliest developmental point may help early risk stratification and novel intervention development.

Neighborhood Crime and Externalizing Behavior in Toddlers: A Longitudinal Study With Neonatal fMRI and Parenting.

OBJECTIVE: Prenatal exposure to neighborhood crime has been associated with weaker neonatal frontolimbic connectivity; however, associations with early childhood behavior remain unclear. We hypothesized that living in a high-crime neighborhood would be related to higher externalizing symptoms at age 1 and 2 years, over and above other adversities, and that neonatal frontolimbic connectivity and observed parenting behaviors at 1 year would mediate this relationship. METHOD: Participants included 399 pregnant women, recruited as part of the Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders (eLABE) study. Geocoded neighborhood crime data was obtained from Applied Geographic Solution. A total of 319 healthy, non-sedated neonates underwent scanning using resting-state functional magnetic resonance imaging (fMRI) on a Prisma 3T scanner and had ≥10 minutes of high-quality data. Infant-Toddler Socioemotional Assessment Externalizing T scores were available for 274 mothers of 1-year-olds and 257 mothers of 2-year-olds. Observed parenting behaviors were available for 202 parent-infant dyads at 1 year. Multilevel and mediation models tested longitudinal associations. RESULTS: Living in a neighborhood with high violent (ß = 0.15, CI = 0.05-0.27, p = .004) and property (ß = 0.10, CI = 0.01-0.20, p = .039) crime was related to more externalizing symptoms at 1 and 2 years, controlling for other adversities. Weaker frontolimbic connectivity was also associated with higher externalizing symptoms at 1 and 2 years. After controlling for other adversities, parenting behaviors mediated the specific association between crime and externalizing symptoms, but frontolimbic connectivity did not. CONCLUSION: These findings provide evidence that early exposure to neighborhood crime and weaker neonatal frontolimbic connectivity may influence later externalizing symptoms, and suggest that parenting may be an early intervention target for families in high-crime areas. DIVERSITY & INCLUSION STATEMENT: We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Neonatal neural responses to novelty related to behavioral inhibition at 1 year.

Behavioral inhibition (BI), an early-life temperament characterized by vigilant responses to novelty, is a risk factor for anxiety disorders. In this study, we investigated whether differences in neonatal brain responses to infrequent auditory stimuli relate to children's BI at 1 year of age. Using functional magnetic resonance imaging (fMRI), we collected blood-oxygen-level-dependent (BOLD) data from N = 45 full-term, sleeping neonates during an adapted auditory oddball paradigm and measured BI from n = 27 of these children 1 year later using an observational assessment. Whole-brain analyses corrected for multiple comparisons identified 46 neonatal brain regions producing novelty-evoked BOLD responses associated with children's BI scores at 1 year of age. More than half of these regions (n = 24, 52%) were in prefrontal cortex, falling primarily within regions of the default mode or frontoparietal networks or in ventromedial/orbitofrontal regions without network assignments. Hierarchical clustering of the regions based on their patterns of association with BI resulted in two groups with distinct anatomical, network, and response-timing profiles. The first group, located primarily in subcortical and temporal regions, tended to produce larger early oddball responses among infants with lower subsequent BI. The second group, located primarily in prefrontal cortex, produced larger early oddball responses among infants with higher subsequent BI. These results provide preliminary insights into brain regions engaged by novelty in infants that may relate to later BI. The findings may inform understanding of anxiety disorders and guide future research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Functional parcellation of the neonatal brain.

The cerebral cortex is organized into distinct but interconnected cortical areas, which can be defined by abrupt differences in patterns of resting state functional connectivity (FC) across the cortical surface. Such parcellations of the cortex have been derived in adults and older infants, but there is no widely used surface parcellation available for the neonatal brain. Here, we first demonstrate that adult- and older infant-derived parcels are a poor fit with neonatal data, emphasizing the need for neonatal-specific parcels. We next derive a set of 283 cortical surface parcels from a sample of n=261 neonates. These parcels have highly homogenous FC patterns and are validated using three external neonatal datasets. The Infomap algorithm is used to assign functional network identities to each parcel, and derived networks are consistent with prior work in neonates. The proposed parcellation may represent neonatal cortical areas and provides a powerful tool for neonatal neuroimaging studies.

Sleep and circadian rhythms during pregnancy, social disadvantage, and alterations in brain development in neonates.

Pregnant women in poverty may be especially likely to experience sleep and circadian rhythm disturbances, which may have downstream effects on fetal neurodevelopment. However, the associations between sleep and circadian rhythm disturbances, social disadvantage during pregnancy, and neonatal brain structure remains poorly understood. The current study explored the association between maternal sleep and circadian rhythm disturbances during pregnancy and neonatal brain outcomes, examining sleep and circadian rhythm disturbances as a mediator of the effect of social disadvantage during pregnancy on infant structural brain outcomes. The study included 148 mother-infant dyads, recruited during early pregnancy, who had both actigraphy and neuroimaging data. Mothers' sleep was assessed throughout their pregnancy using actigraphy, and neonates underwent brain magnetic resonance imaging in the first weeks of life. Neonatal structural brain outcomes included cortical gray matter, subcortical gray matter, and white matter volumes along with a measure of the total surface area of the cortex. Neonates of mothers who experienced greater inter-daily deviations in sleep duration had smaller total cortical gray and white matter volumes and reduced cortical surface areas. Neonates of mothers who had higher levels of circadian misalignment and later sleep timing during pregnancy showed smaller subcortical gray matter volumes. Inter-daily deviations in sleep duration during pregnancy mediated the association between maternal social disadvantage and neonatal structural brain outcomes. Findings highlight the importance of regularity and rhythmicity in sleep schedules during pregnancy and bring to light the role of chronodisruption as a potential mechanism underlying the deleterious neurodevelopmental effects of prenatal adversity. RESEARCH HIGHLIGHTS: Social disadvantage was associated with sleep and circadian rhythm disturbances during pregnancy, including later sleep schedules, increased variability in sleep duration, circadian misalignment, and a higher proportion of the sleep period spent awake. Maternal sleep and circadian rhythm disturbances during pregnancy were associated with decreased brain volume and reduced cortical surface area in neonates. Maternal inter-daily deviations in sleep duration during pregnancy mediated the association between social disadvantage and neonatal brain volume and cortical surface area.

The Association Between Maternal Cortisol and Infant Amygdala Volume Is Moderated by Socioeconomic Status.

Background: It has been well established that socioeconomic status is associated with mental and physical health as well as brain development, with emerging data suggesting that these relationships begin in utero. However, less is known about how prenatal socioeconomic environments interact with the gestational environment to affect neonatal brain volume. Methods: Maternal cortisol output measured at each trimester of pregnancy and neonatal brain structure were assessed in 241 mother-infant dyads. We examined associations between the trajectory of maternal cortisol output across pregnancy and volumes of cortisol receptor-rich regions of the brain, including the amygdala, hippocampus, medial prefrontal cortex, and caudate. Given the known effects of poverty on infant brain structure, socioeconomic disadvantage was included as a moderating variable. Results: Neonatal amygdala volume was predicted by an interaction between maternal cortisol output across pregnancy and socioeconomic disadvantage (standardized ß = -0.31, p < .001), controlling for postmenstrual age at scan, infant sex, and total gray matter volume. Notably, amygdala volumes were positively associated with maternal cortisol for infants with maternal disadvantage scores 1 standard deviation below the mean (i.e., less disadvantage) (simple slope = 123.36, p < .01), while the association was negative in infants with maternal disadvantage 1 standard deviation above the mean (i.e., more disadvantage) (simple slope = -82.70, p = .02). Individuals with disadvantage scores at the mean showed no association, and there were no significant interactions in the other brain regions examined. Conclusions: These data suggest that fetal development of the amygdala is differentially affected by maternal cortisol production at varying levels of socioeconomic advantage.

Prenatal cannabis exposure is associated with localized brain differences that partially mediate associations with increased adolescent psychopathology.

Prenatal cannabis exposure (PCE) is associated with mental health problems, but the neurobiological mechanisms remain unknown. We find that PCE is associated with localized differences across neuroimaging metrics that longitudinally mediate associations with mental health in adolescence (n=9,322-10,186). Differences in brain development may contribute to PCE-related variability in adolescent mental health.

Gabapentin as Adjunctive Therapy in Neonatal Opioid Withdrawal Syndrome: A Case Series.

OBJECTIVE: We describe a single center experience with gabapentin as adjunctive therapy in infants with neonatal opioid withdrawal syndrome (NOWS). METHODS: We performed a retrospective chart review of infants receiving gabapentin for NOWS. Data points collected included patient's sex, gestational age, maternal opioid exposure, NOWS medication dosing and length of therapy, number of failed wean attempts, time to successful morphine wean and duration of morphine wean, length of stay in the neonatal intensive care unit (NICU), and NOWS medications at discharge. RESULTS: Six infants received gabapentin as adjunctive treatment for NOWS. All infants failed 2-4 morphine weans before initiation of gabapentin despite the addition of clonidine. All infants that received gabapentin were successfully weaned off morphine. The time to wean off morphine after gabapentin initiation varied from 4-35 days. Maximum gabapentin doses ranged from 15 - 42.7 mg/kg/day. Five infants were discharged from the NICU on gabapentin. CONCLUSIONS: Gabapentin appeared to facilitate successful morphine weans in six patients with NOWS who were previously unable to wean despite the initiation of clonidine.

Social and psychological adversity are associated with distinct mother and infant gut microbiome variations.

Health disparities are driven by underlying social disadvantage and psychosocial stressors. However, how social disadvantage and psychosocial stressors lead to adverse health outcomes is unclear, particularly when exposure begins prenatally. Variations in the gut microbiome and circulating proinflammatory cytokines offer potential mechanistic pathways. Here, we interrogate the gut microbiome of mother-child dyads to compare high-versus-low prenatal social disadvantage, psychosocial stressors and maternal circulating cytokine cohorts (prospective case-control study design using gut microbiomes from 121 dyads profiled with 16 S rRNA sequencing and 89 dyads with shotgun metagenomic sequencing). Gut microbiome characteristics significantly predictive of social disadvantage and psychosocial stressors in the mothers and children indicate that different discriminatory taxa and related pathways are involved, including many species of Bifidobacterium and related pathways across several comparisons. The lowest inter-individual gut microbiome similarity was observed among high-social disadvantage/high-psychosocial stressors mothers, suggesting distinct environmental exposures driving a diverging gut microbiome assembly compared to low-social disadvantage/low-psychosocial stressors controls (P = 3.5 × 10-5 for social disadvantage, P = 2.7 × 10-15 for psychosocial stressors). Children's gut metagenome profiles at 4 months also significantly predicted high/low maternal prenatal IL-6 (P = 0.029), with many bacterial species overlapping those identified by social disadvantage and psychosocial stressors. These differences, based on maternal social and psychological status during a critical developmental window early in life, offer potentially modifiable targets to mitigate health inequities.

How penalizing substance use in pregnancy affects treatment and research: a qualitative examination of researchers' perspectives.

Introduction: Laws regulating substance use in pregnancy are changing and may have unintended consequences on scientific efforts to address the opioid epidemic. Yet, how these laws affect care and research is poorly understood. Methods: We conducted semi-structured qualitative interviews using purposive and snowball sampling of researchers who have engaged pregnant people experiencing substance use. We explored views on laws governing substance use in pregnancy and legal reform possibilities. Interviews were double coded. Data were examined using thematic analysis. Results: We interviewed 22 researchers (response rate: 71 per cent) and identified four themes: (i) harms of punitive laws, (ii) negative legal impacts on research, (iii) proposals for legal reform, and (iv) activism over time. Discussion: Researchers view laws penalizing substance use during pregnancy as failing to treat addiction as a disease and harming pregnant people and families. Respondents routinely made scientific compromises to protect participants. While some have successfully advocated for legal reform, ongoing advocacy is needed. Conclusion: Adverse impacts from criminalizing substance use during pregnancy extend to research on this common and stigmatized problem. Rather than penalizing substance use in pregnancy, laws should approach addiction as a medical issue and support scientific efforts to improve outcomes for affected families.

Associations Between Preterm Birth, Inhibitory Control-Implicated Brain Regions and Tracts, and Inhibitory Control Task Performance in Children: Consideration of Socioeconomic Context.

Preterm birth (PTB) is associated with increased risk for unfavorable outcomes such as deficits in attentional control and related brain structure alterations. Crucially, PTB is more likely to occur within the context of poverty. The current study examined associations between PTB and inhibitory control (IC) implicated brain regions/tracts and task performance, as well as the moderating role of early life poverty on the relation between PTB and IC-implicated regions/tracts/task performance. 2,899 children from the ABCD study were sampled for this study. Mixed effects models examined the relation between PTB and subsequent IC performance as well as prefrontal gray matter volume, white matter fractional anisotropy (FA), and mean diffusivity (MD). Household income was examined as a moderator. PTB was significantly associated with less improvement in IC task performance over time and decreased FA in left uncinate fasciculus (UF) and cingulum bundle (CB). Early life poverty moderated the relation between PTB and both CB FA and UF MD.

A somato-cognitive action network alternates with effector regions in motor cortex.

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations1,2, despite evidence for concentric functional zones3 and maps of complex actions4. Here, using precision functional magnetic resonance imaging (fMRI) methods, we find that the classic homunculus is interrupted by regions with distinct connectivity, structure and function, alternating with effector-specific (foot, hand and mouth) areas. These inter-effector regions exhibit decreased cortical thickness and strong functional connectivity to each other, as well as to the cingulo-opercular network (CON), critical for action5 and physiological control6, arousal7, errors8 and pain9. This interdigitation of action control-linked and motor effector regions was verified in the three largest fMRI datasets. Macaque and pediatric (newborn, infant and child) precision fMRI suggested cross-species homologues and developmental precursors of the inter-effector system. A battery of motor and action fMRI tasks documented concentric effector somatotopies, separated by the CON-linked inter-effector regions. The inter-effectors lacked movement specificity and co-activated during action planning (coordination of hands and feet) and axial body movement (such as of the abdomen or eyebrows). These results, together with previous studies demonstrating stimulation-evoked complex actions4 and connectivity to internal organs10 such as the adrenal medulla, suggest that M1 is punctuated by a system for whole-body action planning, the somato-cognitive action network (SCAN). In M1, two parallel systems intertwine, forming an integrate-isolate pattern: effector-specific regions (foot, hand and mouth) for isolating fine motor control and the SCAN for integrating goals, physiology and body movement.