Talk:Neural System - Fetal

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Cite this page: Hill, M.A. (2020, September 24) Embryology Neural System - Fetal. Retrieved from


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

Pediatr Res. 2018 May;83(5):976-981. doi: 10.1038/pr.2018.4. Epub 2018 Feb 7.

Matthews LG1, Walsh BH1, Knutsen C2, Neil JJ3, Smyser CD2, Rogers CE2, Inder TE1.


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. PMID: 29320484 DOI: 10.1038/pr.2018.4


Exploring the role of white matter connectivity in cortex maturation

PLoS One. 2017 May 17;12(5):e0177466. doi: 10.1371/journal.pone.0177466. eCollection 2017.

Friedrichs-Maeder CL1, Griffa A1,2, Schneider J3,4, Hüppi PS5, Truttmann A3, Hagmann P1,2.


The maturation of the cortical gray matter (GM) and white matter (WM) are described as sequential processes following multiple, but distinct rules. However, neither the mechanisms driving brain maturation processes, nor the relationship between GM and WM maturation are well understood. Here we use connectomics and two MRI measures reflecting maturation related changes in cerebral microstructure, namely the Apparent Diffusion Coefficient (ADC) and the T1 relaxation time (T1), to study brain development. We report that the advancement of GM and WM maturation are inter-related and depend on the underlying brain connectivity architecture. Particularly, GM regions and their incident WM connections show corresponding maturation levels, which is also observed for GM regions connected through a WM tract. Based on these observations, we propose a simple computational model supporting a key role for the connectome in propagating maturation signals sequentially from external stimuli, through primary sensory structures to higher order functional cortices. PMID: 28545040 PMCID: PMC5435226 DOI: 10.1371/journal.pone.0177466

The Lateral Temporal Lobe in Early Human Life

J Neuropathol Exp Neurol. 2017 Jun 1;76(6):424-438. doi: 10.1093/jnen/nlx026.

Goldstein IS1, Erickson DJ1, Sleeper LA1, Haynes RL1, Kinney HC1.


Abnormalities of lateral temporal lobe development are associated with a spectrum of genetic and environmental pathologic processes, but more normative data are needed for a better understanding of gyrification in this brain region. Here, we begin to establish guidelines for the analysis of the lateral temporal lobe in humans in early life. We present quantitative methods for measuring gyrification at autopsy using photographs of the gross brain and simple computer-based quantitative tools in a cohort of 28 brains ranging in age from 27 to 70 postconceptional weeks (end of infancy). We provide normative ranges for different indices of gyrification and identify a constellation of qualitative features that should also be considered in these analyses. The ratio of the temporal area to the whole brain area increased dramatically in the second half of gestation, but then decelerated after birth before increasing linearly around 50 postconceptional weeks. Tertiary gyrification continued beyond birth in a linear process through infancy with considerable variation in patterns. Analysis of 2 brains with gyral disorders of the lateral temporal lobe demonstrated proof-of-principle that the proposed methods are of diagnostic value. These guidelines are proposed for assessments of temporal lobe pathology in pediatric brains in early life. KEYWORDS: Down syndrome; Gyrification; Operculum; Sylvian fissure; Temporal lobe pathology PMID: 28498956 DOI: 10.1093/jnen/nlx026


Are Developmental Trajectories of Cortical Folding Comparable Between Cross-sectional Datasets of Fetuses and Preterm Newborns?

Cereb Cortex. 2016 Jul;26(7):3023-35. doi: 10.1093/cercor/bhv123. Epub 2015 Jun 3.

Lefèvre J1, Germanaud D2, Dubois J3, Rousseau F4, de Macedo Santos I5, Angleys H3, Mangin JF5, Hüppi PS6, Girard N7, De Guio F8.


Magnetic resonance imaging has proved to be suitable and efficient for in vivo investigation of the early process of brain gyrification in fetuses and preterm newborns but the question remains as to whether cortical-related measurements derived from both cases are comparable or not. Indeed, the developmental folding trajectories drawn up from both populations have not been compared so far, neither from cross-sectional nor from longitudinal datasets. The present study aimed to compare features of cortical folding between healthy fetuses and early imaged preterm newborns on a cross-sectional basis, over a developmental period critical for the folding process (21-36 weeks of gestational age [GA]). A particular attention was carried out to reduce the methodological biases between the 2 populations. To provide an accurate group comparison, several global parameters characterizing the cortical morphometry were derived. In both groups, those metrics provided good proxies for the dramatic brain growth and cortical folding over this developmental period. Except for the cortical volume and the rate of sulci appearance, they depicted different trajectories in both groups suggesting that the transition from into ex utero has a visible impact on cortical morphology that is at least dependent on the GA at birth in preterm newborns. KEYWORDS: cortical surface; curvature; development of cortical sulci; fetal MRI; in utero; morphometry; premature birth; segmentation PMID: 26045567 DOI: 10.1093/cercor/bhv123

Regional growth and atlasing of the developing human brain

Neuroimage. 2016 Jan 15;125:456-478. doi: 10.1016/j.neuroimage.2015.10.047. Epub 2015 Oct 21.

Makropoulos A1, Aljabar P2, Wright R3, Hüning B4, Merchant N2, Arichi T2, Tusor N2, Hajnal JV2, Edwards AD2, Counsell SJ5, Rueckert D3.

Abstract Detailed morphometric analysis of the neonatal brain is required to characterise brain development and define neuroimaging biomarkers related to impaired brain growth. Accurate automatic segmentation of neonatal brain MRI is a prerequisite to analyse large datasets. We have previously presented an accurate and robust automatic segmentation technique for parcellating the neonatal brain into multiple cortical and subcortical regions. In this study, we further extend our segmentation method to detect cortical sulci and provide a detailed delineation of the cortical ribbon. These detailed segmentations are used to build a 4-dimensional spatio-temporal structural atlas of the brain for 82 cortical and subcortical structures throughout this developmental period. We employ the algorithm to segment an extensive database of 420 MR images of the developing brain, from 27 to 45weeks post-menstrual age at imaging. Regional volumetric and cortical surface measurements are derived and used to investigate brain growth and development during this critical period and to assess the impact of immaturity at birth. Whole brain volume, the absolute volume of all structures studied, cortical curvature and cortical surface area increased with increasing age at scan. Relative volumes of cortical grey matter, cerebellum and cerebrospinal fluid increased with age at scan, while relative volumes of white matter, ventricles, brainstem and basal ganglia and thalami decreased. Preterm infants at term had smaller whole brain volumes, reduced regional white matter and cortical and subcortical grey matter volumes, and reduced cortical surface area compared with term born controls, while ventricular volume was greater in the preterm group. Increasing prematurity at birth was associated with a reduction in total and regional white matter, cortical and subcortical grey matter volume, an increase in ventricular volume, and reduced cortical surface area. PMID: 26499811 PMCID: PMC4692521 DOI: 10.1016/j.neuroimage.2015.10.047


Local tissue growth patterns underlying normal fetal human brain gyrification quantified in utero

J Neurosci. 2011 Feb 23;31(8):2878-87.

Rajagopalan V, Scott J, Habas PA, Kim K, Corbett-Detig J, Rousseau F, Barkovich AJ, Glenn OA, Studholme C. Source Biomedical Image Computing Group, Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, California 94143-0628, USA.


Existing knowledge of growth patterns in the living fetal human brain is based upon in utero imaging studies by magnetic resonance imaging (MRI) and ultrasound, which describe overall growth and provide mainly qualitative findings. However, formation of the complex folded cortical structure of the adult brain requires, in part, differential rates of regional tissue growth. To better understand these local tissue growth patterns, we applied recent advances in fetal MRI motion correction and computational image analysis techniques to 40 normal fetal human brains covering a period of primary sulcal formation (20-28 gestational weeks). Growth patterns were mapped by quantifying tissue locations that were expanding more or less quickly than the overall cerebral growth rate, which reveal increasing structural complexity. We detected increased local relative growth rates in the formation of the precentral and postcentral gyri, right superior temporal gyrus, and opercula, which differentiated between the constant growth rate in underlying cerebral mantle and the accelerating rate in the cortical plate undergoing folding. Analysis focused on the cortical plate revealed greater volume increases in parietal and occipital regions compared to the frontal lobe. Cortical plate growth patterns constrained to narrower age ranges showed that gyrification, reflected by greater growth rates, was more pronounced after 24 gestational weeks. Local hemispheric volume asymmetry was located in the posterior peri-Sylvian area associated with structural lateralization in the mature brain. These maps of fetal brain growth patterns construct a spatially specific baseline of developmental biomarkers with which to correlate abnormal development in the human.

PMID 21414909 PMC3093305

Identification and Analysis of Intermediate Size Noncoding RNAs in the Human Fetal Brain

PLoS One. 2011;6(7):e21652. Epub 2011 Jul 18.

Yan D, He D, He S, Chen X, Fan Z, Chen R. Source Bioinformatics Laboratory and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China.


The involvement of noncoding RNAs (ncRNAs) in the development of the human brain remains largely unknown. Applying a cloning strategy for detection of intermediate size (50-500 nt) ncRNAs (is-ncRNAs) we have identified 82 novel transcripts in human fetal brain tissue. Most of the novel is-ncRNAs are not well conserved in vertebrates, and several transcripts were only found in primates. Northern blot and microarray analysis indicated considerable variation in expression across human fetal brain development stages and fetal tissues for both novel and known is-ncRNAs. Expression of several of the novel is-ncRNAs was conspicuously absent in one or two brain cancer cell lines, and transient overexpression of some transcripts in cancer cells significantly inhibited cell proliferation. Overall, our results suggest that is-ncRNAs play important roles in the development and tumorigenesis of human brain.

PMID 21789175


Development of the fetal spinal cord: time of ascendance of the normal conus medullaris as detected by sonography

Zalel Y, Lehavi O, Aizenstein O, Achiron R. J Ultrasound Med. 2006 Nov;25(11):1397-401; quiz 1402-3.

OBJECTIVE: The purpose of this study was to perform high-resolution sonographic examinations to determine the normal anatomic relationship of the conus medullaris (CM) of the spinal cord with the vertebral column during different stages of gestation.

METHODS: In this prospective study, fetal sonographic evaluations were performed between 13 and 40 weeks' gestation. Transvaginal probes (7.5-8 MHz) or abdominal probes (5-8 MHz) were used, depending on gestational age and position of the fetus. The CM was located in coronal longitudinal sections. The positions of the kidneys and lumbosacral junction and the origin of the ribs determined the location of the vertebrae. The locations of the CM were divided into 5 groups according to their positions relative to the vertebrae.

RESULTS: A total of 110 fetuses between 13 and 40 weeks' gestation were studied. Between 13 and 18 weeks' gestation, the CM was situated at the level of the L4 vertebra, or more caudally, in 100% of the fetuses. At term, all fetuses showed the CM above L2. A distinct ascent of the CM was detected between 13 and 40 weeks' gestation. The results were statistically significant (P < .0001).

CONCLUSIONS: A distinguishable ascent of the CM in relation to the vertebral column during fetal life was detected.

PMID: 17060425

Vagus, hypoglossal, and median nerves in human development

Int J Neurosci. 2007 Apr;117(4):453-64.

Liang Y, Fang M, Li J, Wai MS, Lam WP, Yew DT.

Institute of Cell Biology, Medical College of Zhejiang University, Hangzhou, Zhejiang, China. Abstract In spite of the wealth of literature on the changes of the neurons in development of the brainstem and the spinal cord in vertebrates, the alterations of the cranial nerves and somatic nerves during the prenatal period was largely neglected. Particularly in humans, little information was available. The article reports the changes in the vagus, hypoglossal, and median nerves in the fetus and term babies. The changes of proportion of different-sized nerve fibers are documented. The patterns were different in the three nerves and the hypoglossal nerve seemed to show "pruning" of fibers during this period.

PMID: 17365128