Prenatal Exposure to Early Life Adversity and Neonatal Brain Volumes at Birth

Importance: Exposure to early life adversity alters the structural development of key brain regions underlying neurodevelopmental impairments. The extent that prenatal exposure to life adversity alters structure at birth remains poorly understood. Objective: To determine if prenatal exposure to maternal social advantage and psychosocial distress alters global and regional brain volumes and cortical folding in the first weeks of life. Design: A prospective, longitudinal study of sociodemographically-diverse mothers recruited in the first trimester of pregnancy and their infants who underwent brain magnetic resonance imaging scan in the first weeks of life. Setting: Mothers were recruited from local obstetric clinics from 2017-2020. Participants: Of 399 mother-infant dyads prospectively recruited into the parent study, 280 healthy, term-born infants (47% female, mean postmenstrual age at scan 42 weeks) were eligible for inclusion. Exposures: Maternal social advantage and psychosocial distress in pregnancy. Main Measures and Outcomes: Two measures of latent constructs were created using Confirmatory Factor Analyses spanning Maternal Social Advantage (Income to Needs ratio, Area Deprivation Index, Healthy Eating Index, education level, insurance status) and Psychosocial Stress (Perceived Stress Scale, Edinburgh Postnatal Depression Scale, Everyday Discrimination Scale, Stress and Adversity Inventory). Neonatal cortical and subcortical gray matter, white matter, cerebellar, hippocampus, and amygdala volumes were generated using semi-automated age-specific segmentation pipelines. Results: After covariate adjustment and multiple comparisons correction, greater social disadvantage (i.e., lower Advantage values) was associated with reduced cortical gray matter (p=.03), subcortical gray matter (p=.008), and white matter (p=.004) volumes and cortical folding (p=.001). Psychosocial Stress was not related to neonatal brain metrics. While social disadvantage was associated with smaller absolute volumes of the bilateral hippocampi and amygdalae, after correcting for total brain volume, there were no regional effects. Conclusions and Relevance: Prenatal exposure to social disadvantage is associated with global reductions in brain volumes and cortical folding at birth. No regional specificity for the hippocampus or amygdala was detected. Results highlight that the deleterious effects of poverty begin in utero and are evident in the first weeks of life. These findings emphasize that preventative interventions to support fetal brain development should address socioeconomic hardships for expectant parents.

The retrocalcarine sulcus maps different retinotopic representations in macaques and humans

Primate cerebral cortex is highly convoluted with much of the cortical surface buried in sulcal folds. The origins of cortical folding and its functional relevance have been a major focus of systems and cognitive neuroscience, especially when considering stereotyped patterns of cortical folding that are shared across individuals within a primate species and across multiple species. However, foundational questions regarding organizing principles shared across species remain unanswered. Taking a cross-species comparative approach with a careful consideration of historical observations, we investigate cortical folding relative to primary visual cortex (area V1). We identify two macroanatomical structures—the retrocalcarine and external calcarine sulci—in 24 humans and 6 macaque monkeys. We show that within species, these sulci are identifiable in all individuals, fall on a similar part of the V1 retinotopic map, and thus, serve as anatomical landmarks predictive of functional organization. Yet, across species, the underlying eccentricity representations corresponding to these macroanatomical structures differ strikingly across humans and macaques. Thus, the correspondence between retinotopic representation and cortical folding for an evolutionarily old structure like V1 is species-specific and suggests potential differences in developmental and experiential constraints across primates.

A model of tension-induced fiber growth predicts white matter organization during brain folding

The past decade has experienced renewed interest in the physical processes that fold the developing cerebral cortex. Biomechanical models and experiments suggest that growth of the cortex, outpacing growth of underlying subcortical tissue (prospective white matter), is sufficient to induce folding. However, current models do not explain the well-established links between white matter organization and fold morphology, nor do they consider subcortical remodeling that occurs during the period of folding. Here we propose a framework by which cortical folding may induce subcortical fiber growth and organization. Simulations incorporating stress-induced fiber elongation indicate that subcortical stresses resulting from folding are sufficient to induce stereotyped fiber organization beneath gyri and sulci. Model predictions are supported by high-resolution ex vivo diffusion tensor imaging of the developing rhesus macaque brain. Together, results provide support for the theory of cortical growth-induced folding and indicate that mechanical feedback plays a significant role in brain connectivity.

What brain abnormalities can magnetic resonance imaging detect in foetal and early neonatal spina bifida: a systematic review

Purpose Open spina bifida (OSB) encompasses a wide spectrum of intracranial abnormalities. With foetal surgery as a new treatment option, robust intracranial imaging is important for comprehensive preoperative evaluation and prognostication. We aimed to determine the incidence of infratentorial and supratentorial findings detected by magnetic resonance imaging (MRI) alone and MRI compared to ultrasound. Methods Two systematic reviews comparing MRI to ultrasound and MRI alone were conducted on MEDLINE, EMBASE, and Cochrane databases identifying studies of foetal OSB from 2000 to 2020. Intracranial imaging findings were analysed at ≤ 26 or > 26 weeks gestation and neonates (≤ 28 days). Data was independently extracted by two reviewers and meta-analysis was performed where possible. Results Thirty-six studies reported brain abnormalities detected by MRI alone in patients who previously had an ultrasound. Callosal dysgenesis was identified in 4/29 cases (2 foetuses ≤ 26 weeks, 1 foetus under any gestation, and 1 neonate ≤ 28 days) (15.1%, CI:5.7–34.3%). Heterotopia was identified in 7/40 foetuses ≤ 26 weeks (19.8%, CI:7.7–42.2%), 9/36 foetuses > 26 weeks (25.3%, CI:13.7–41.9%), and 64/250 neonates ≤ 28 days (26.9%, CI:15.3–42.8%). Additional abnormalities included aberrant cortical folding and other Chiari II malformation findings such as lower cervicomedullary kink level, tectal beaking, and hypoplastic tentorium. Eight studies compared MRI directly to ultrasound, but due to reporting inconsistencies, it was not possible to meta-analyse. Conclusion MRI is able to detect anomalies hitherto underestimated in foetal OSB which may be important for case selection. In view of increasing prenatal OSB surgery, further studies are required to assess developmental consequences of these findings.