Complex Trajectories of Brain Development in the Healthy Human Fetus

Abstract

This study characterizes global and hemispheric brain growth in healthy human fetuses during the second half of pregnancy using three-dimensional MRI techniques. We studied 166 healthy fetuses that underwent MRI between 18 and 39 completed weeks gestation. We created three-dimensional high-resolution reconstructions of the brain and calculated volumes for left and right cortical gray matter (CGM), fetal white matter (FWM), deep subcortical structures (DSS), and the cerebellum. We calculated the rate of growth for each tissue class according to gestational age and described patterns of hemispheric growth. Each brain region demonstrated major increases in volume during the second half of gestation, the most pronounced being the cerebellum (34-fold), followed by FWM (22-fold), CGM (21-fold), and DSS (10-fold). The left cerebellar hemisphere, CGM, and DSS had larger volumes early in gestation, but these equalized by term. It has been increasingly recognized that brain asymmetry evolves throughout the human life span. Advanced quantitative MRI provides noninvasive measurements of early structural asymmetry between the left and right fetal brain that may inform functional and behavioral laterality differences seen in children and young adulthood.

Subtle left-right asymmetry of gene expression profiles in embryonic and foetal human brains

“…Possible reasons for these brain asymmetries are still debated, but various cognitive 40 disorders can involve deviations from typical asymmetry patterns, suggesting that laterality is an 41 important aspect of optimal brain development 11-13 . 42 Anatomical laterality of various brain structures becomes apparent in utero [14][15][16][17][18][19] , with the earliest 43 observation at just 11 post conception weeks (pcw), concerning the choroid plexuses (left larger than 44 right on average 14 ). In addition, lateralized arm movements have been observed as early as 8 pcw 20,21 .…”

Identification of De Novo JAK2 and MAPK7 Mutations Related to Autism Spectrum Disorder Using Whole-Exome Sequencing in a Chinese Child and Adolescent Trio-Based Sample

“…Furthermore, the JAK2 gene was found to have the highest expression level in the CBC, playing a central role in cognitive and emotional processing, which are key deficits in autism and other neuropsychiatric disorders (Menashe et al 2013;Wang et al 2014). The degrees of variation in expression levels in different brain regions are similar for MAPK7, and the peak expression levels of this gene appear in the mid-embryo phase, which involves a rapid increase in the volume of the cortical plate and the surface of the human brain (Clouchoux et al 2012;Andescavage et al 2017). The changes in cortical thickness, especially the volume gain of the gray matter during brain development associated with language development, social cognition, and behavioral control, are driven by a lack of typical age-related increase in cortical thickness and play an important role in early childhood autism (Smith et al 2016).…”

Brain growth in the NICU: critical periods of tissue-specific expansion

“…This hypothesis is corroborated by recent reports of rapid fetal cortical GM growth in the third trimester compared with WM (28), as well as evidence of marked increases in fetal cortical GM growth alongside decreases in fetal WM and cerebellar growth during the third trimester (28–39 weeks) compared with the second trimester (18–27 weeks). (1) In their study, Andescavage and colleagues demonstrated fetal WM as the primary initial contributor to cerebral development peaking between 29 and 30 weeks’ gestation, at which point relative cortical GM volume begins to rapidly increase. (1) For infants born VPT, this period of accelerated growth taking place ex-utero is susceptible to disruption by exposures and stressors in the NICU, (2, 29) and our previous work suggests that regions of rapid cortical expansion are likely to be more sensitive to postnatal experience and insult.…”

“…(1) In their study, Andescavage and colleagues demonstrated fetal WM as the primary initial contributor to cerebral development peaking between 29 and 30 weeks’ gestation, at which point relative cortical GM volume begins to rapidly increase. (1) For infants born VPT, this period of accelerated growth taking place ex-utero is susceptible to disruption by exposures and stressors in the NICU, (2, 29) and our previous work suggests that regions of rapid cortical expansion are likely to be more sensitive to postnatal experience and insult. (30) Importantly, disruptions to normal cortical maturational trajectories during the late third trimester have been postulated to underpin the neurodevelopmental impairments seen in preterm infants.…”

“…(1) Importantly, rates of brain growth are not consistent across this period, with cross-sectional fetal magnetic resonance imaging (MRI) studies demonstrating that the greatest period of expansion occurs during the third trimester. (1) For very preterm (VPT; born at <30 weeks’ gestation) infants, this critical period of brain development will occur in the ex-utero environment, with growing concern that environmental factors in the neonatal intensive care unit (NICU) may deleteriously impact infant brain development, along with associated implications for neurodevelopmental outcomes. (2)…”