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Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representations 1,2 , despite evidence for concentric functional zones 3 and maps of complex actions 4 . 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 action 5 and physiological control 6 , arousal 7 , errors 8 and pain 9 . 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 actions 4 and connectivity to internal organs 10 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., (© 2023. The Author(s).)

Objectives: Examine maternal and paternal ADHD and ASD symptoms in relation to very preterm (VPT) and full-term (FT) children's ADHD and ASD symptoms., Study Design: In this longitudinal study, maternal- and teacher-report of child ADHD and ASD symptoms were obtained for 119 children (VPT = 79, FT = 40) at age 5-years using the Conner's Rating Scale-Revised (CRS-R) and Social Responsiveness Scale-2 (SRS-2). A biological parent completed self- and observer-report CRS-R and SRS-2, and measures of mood/affect, stress, and social support to assess psychosocial distress. Data were analyzed using mixed-effect models adjusted for covariates., Results: Child ADHD symptoms were associated with VPT birth, maternal distress, and maternal ADHD symptoms (p ≤ 0.02), and paternal ADHD symptoms (p < 0.001). Regarding ASD, VPT birth and parental ASD symptoms were associated with child ASD symptoms (p ≤ 0.009). Parental symptoms and birth group had no interaction., Conclusions: VPT birth and parental psychopathology represent independent risks for ADHD and ASD., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To examine 5-year outcomes in children enrolled in a pilot randomized controlled trial of a high loading dose of caffeine after preterm birth., Study Design: Seventy-four very low birth weight neonates were randomized within the first 24 h of life to receive a high (80 mg/kg) or standard (20 mg/kg) loading dose of caffeine citrate. At 5 years of age, we conducted standardized neurodevelopmental tests and collected parent reports of child socioemotional problems., Result: Seventy-four percent of survivors returned for follow up. Children obtained similar scores on neurodevelopmental and socioemotional evaluations. There was no difference in the incidence of any neurodevelopmental delay after controlling for confounding factors., Conclusion: Five-year follow up of a pilot trial of high loading dose caffeine citrate documented no profound impacts on childhood neurodevelopment or socioemotional outcome., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Objective: To characterize the lived experiences of stress associated with having a preterm infant hospitalized in the NICU among Black and Hispanic mothers., Methods: We performed a qualitative content analysis of secondary data from two prior studies that included 39 in-depth interviews with Black and Hispanic mothers of preterm infants at 3 U.S. NICUs. We used a constant comparative method to select important concepts and to develop codes and subsequent themes., Results: Black and Hispanic mothers described stressors in the following domains and categories: Individual (feeling overwhelmed, postpartum medical complications, previous stressful life events, competing priorities); Hospital (perceived poor quality of care, provider communication issues, logistical issues); Community (lack of social supports, lack of financial resources, work challenges)., Conclusions: The findings of this study suggest that stressors both inside and outside of the hospital affect the lived experiences of stress by Black and Hispanic mothers during NICU hospitalization., (© 2021. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: The aim of the study was to describe and contrast the brain development and outcome among very preterm infants that were and were not exposed to surgery requiring general anesthesia prior to term equivalent age (TEA)., Methods: Preterm infants born ≤30 weeks' gestation who did (n = 25) and did not (n = 59) have surgery requiring general anesthesia during the preterm period were studied. At TEA, infants had MRI scans performed with measures of brain tissue volumes, cortical surface area, Gyrification Index, and white matter microstructure. Neurodevelopmental follow-up with the Bayley Scales of Infant and Toddler Development, Third Edition was undertaken at 2 years of corrected age. Multivariate models, adjusted for clinical and social risk factors, were used to compare the groups., Results: After controlling for clinical and social variables, preterm infants exposed to surgical anesthesia demonstrated decreased relative white matter volumes at TEA and lower cognitive and motor composite scores at 2-year follow-up. Those with longer surgical exposure demonstrated the greatest decrease in white matter volumes and lower cognitive and motor outcomes at age 2 years., Conclusions: Very preterm infants who required surgery during the preterm period had lower white mater volumes at TEA and worse neurodevelopmental outcome at age 2 years., Impact: In very preterm infants, there is an association between surgery requiring general anesthesia during the preterm period and reduced white mater volume on MRI at TEA and lower cognitive and motor composite scores at age 2 years. It is known that the very preterm infant's brain undergoes rapid growth during the period corresponding to the third trimester. The current study suggests an association between surgery requiring general anesthesia during this period and worse outcomes.

Background: This study examines relationships between neonatal white and gray matter microstructure and neurodevelopment in very preterm (VPT) infants (≤30 weeks gestation) with high-grade brain injury (BI)., Methods: Term-equivalent diffusion tensor magnetic resonance imaging data were obtained in 32 VPT infants with high-grade BI spanning grade III/IV intraventricular hemorrhage, post-hemorrhagic hydrocephalus (PHH), and cystic periventricular leukomalacia (BI group); 69 VPT infants without high-grade injury (VPT group); and 55 term-born infants. The Bayley-III assessed neurodevelopmental outcomes at age 2 years., Results: BI infants had lower fractional anisotropy (FA) in the posterior limb of the internal capsule (PLIC), cingulum, and corpus callosum, and higher mean diffusivity (MD) in the optic radiations and cingulum than VPT infants. PHH was associated with higher MD in the optic radiations and left PLIC, and higher FA in the right caudate. For BI infants, higher MD in the right optic radiation and lower FA in the right cingulum, PLIC, and corpus callosum were related to motor impairments., Conclusions: BI infants demonstrated altered white and gray matter microstructure in regions affected by injury in a manner dependent upon injury type. PHH infants demonstrated the greatest impairments. Aberrant white matter microstructure was related to motor impairment in BI infants.

ObjectiveTo examine, using serial magnetic resonance imaging (MRI), total and tissue-specific brain growth in very-preterm (VPT) infants during the period that coincides with the early and late stages of the third trimester.MethodsStructural MRI scans were collected from two prospective cohorts of VPT infants (≤30 weeks of gestation). A total of 51 MRI scans from 18 VPT subjects were available for volumetric analysis. Brain tissue was classified into cerebrospinal fluid, cortical gray matter, myelinated and unmyelinated white matter, deep nuclear gray matter, and cerebellum. Nine infants had sufficient serial scans to allow comparison of tissue growth during the periods corresponding to the early and late stages of the third trimester.ResultsTissue-specific differences in ex utero brain growth trajectories were observed in the period corresponding to the third trimester. Most notably, there was a marked increase in cortical gray matter expansion from 34 to 40 weeks of postmenstrual age, emphasizing this critical period of brain development.ConclusionUtilizing serial MRI to document early brain development in VPT infants, this study documents regional differences in brain growth trajectories ex utero during the period corresponding to the first and second half of the third trimester, providing novel insight into the maturational vulnerability of the rapidly expanding cortical gray matter in the NICU.

Background: Preterm infants are at risk for white matter (WM) injury and adverse neurodevelopmental outcomes., Methods: Serial diffusion tensor magnetic resonance imaging data were obtained from very preterm infants (N = 78) born <30 wk gestation imaged up to four times from 26-42 wk postmenstrual age. Slopes were calculated for fractional anisotropy (FA) and mean diffusivity (MD) within regions of interest for infants with ≥2 scans (N = 50). Sixty-five children underwent neurodevelopmental testing at 2 y of age., Results: FA slope for the posterior limb of the internal capsule was greater than other regions. The anterior limb of the internal capsule (ALIC), corpus callosum, and optic radiations demonstrated greater FA slope with increasing gestational age. Infants with patent ductus arteriosus had lower FA slope in the ALIC. MD slope was lower with prolonged ventilation or lack of antenatal steroids. At 2 y of age, lower motor scores were associated with lower FA in the left but higher FA in the right inferior temporal lobe at term-equivalent age. Better social-emotional competence was related to lower FA in the left cingulum bundle., Conclusion: This study demonstrates regional variability in the susceptibility/sensitivity of WM maturation to perinatal factors and relationships between altered diffusion measures and developmental outcomes in preterm neonates.

Objective: Determine the association of prenatal and neonatal infections with neurodevelopmental outcomes in very preterm infants., Study Design: Secondary retrospective analysis of 155 very preterm infants at a single tertiary referral center. General linear or logistic regression models were used to evaluate the association with hospital factors; brain injury, growth and development; and neurobehavioral outcome., Result: Necrotizing enterocolitis with sepsis was associated with reduced transcerebellar diameter (38.3 vs 48.4 mm, P<0.001) and increased left ventricular diameter (12.0 vs 8.0 mm, P=0.005). Sepsis alone was associated with higher diffusivity in the left frontal lobe (1.85 vs 1.68 × 10⁻³ mm² s⁻¹, P=0.001) and right cingulum bundle (1.52 vs 1.45 × 10⁻³ mm 253 s⁻¹, P=0.002). Neurobehavioral outcomes were worse in children exposed to maternal genitourinary infection (cognitive composite: β=-8.8, P=0.001; receptive language score: β=-2.7, P<0.001; language composite: β=-14.9, P<0.001) or histological chorioamnionitis (language composite: β=-8.6, P=0.006), but not neonatal infection., Conclusion: Neonatal infection was associated with changes in brain structure but not with neurobehavioral outcomes, whereas the opposite pattern was observed for maternal genitourinary tract infection. These findings emphasize the potential importance of infections during pregnancy on the neurodevelopmental outcomes of preterm infants.

Objective: Thirty-five percent of women of child-bearing age are obese, and there is evidence that maternal obesity may increase the risk for adverse neurodevelopmental outcome. However, research regarding obesity and neurodevelopment among children born preterm is limited. This study aimed to determine associations between maternal obesity and neurodevelopment in very preterm children at age 2 years., Study Design: Maternal/infant dyads (n=62) born ⩽30 weeks gestation were enrolled in a prospective cohort study at a level-III neonatal intensive care unit. Mothers were classified as obese or non-obese based on pre-pregnancy body mass index. Infants underwent magnetic resonance imaging at term equivalent and developmental testing at age 2. Maternal obesity was investigated for associations with neurodevelopment., Result: Maternal obesity was associated with positive screen for autism (odds ratio=9.88, P=0.002) and lower composite language scores (β=-9.36, (confidence interval=-15.11, -3.61), P=0.002)., Conclusion: Maternal obesity was associated with adverse neurodevelopmental outcome at age 2 in this cohort of very preterm children. This study requires replication, but may support targeted surveillance of infants born to women with maternal obesity.

Objective: We investigated whether particular demographics, maternal psychosocial and infant factors identified mothers of very preterm infants at risk for postpartum depression or anxiety at the time of discharge from a level III urban Neonatal Intensive Care Unit (NICU)., Study Design: A racially diverse cohort of mothers (N=73) of preterm infants (gestational age <30 weeks) completed a comprehensive questionnaire at discharge from the NICU assessing postpartum depression, anxiety and psychosocial and demographic factors. Additionally, infants underwent brain magnetic resonance imaging before discharge., Result: Twenty percent of mothers had clinically significant levels of depression whereas 43% had moderate to severe anxiety. Being married (P<0.01), parental role alteration (P<0.01) and prolonged ventilation (P<0.05) were associated with increased depressive symptoms. No psychosocial, demographics or infant factors, including severity of brain injury, were associated with state anxiety levels., Conclusion: Maternal factors, such as marital status, stress from parental role alteration and infant factors, such as prolonged ventilation, are associated with increased depression. However, clinically significant levels of anxiety are common in mothers of very preterm infants with few identifiable risk factors. These findings support the need for universal screening within the NICU.