Compelling evidence indicates that psychiatric and developmental disorders are generally caused by disruptions in the functional connectivity (FC) of brain networks. Events occurring during development, and in particular during fetal life, have been implicated in the genesis of such disorders. However, the developmental timetable for the emergence of neural FC during human fetal life is unknown. We present the results of resting-state functional magnetic resonance imaging performed in 25 healthy human fetuses in the second and third trimesters of pregnancy (24 to 38 weeks of gestation). We report the presence of bilateral fetal brain FC and regional and age-related variation in FC. Significant bilateral connectivity was evident in half of the 42 areas tested, and the strength of FC between homologous cortical brain regions increased with advancing gestational age. We also observed medial to lateral gradients in fetal functional brain connectivity. These findings improve understanding of human fetal central nervous system development and provide a basis for examining the role of insults during fetal life in the subsequent development of disorders in neural FC.

Formation of operational neural networks is one of the most significant accomplishments of human fetal brain growth. Recent advances in functional magnetic resonance imaging (fMRI) have made it possible to obtain information about brain function during fetal development. Specifically, resting-state fMRI and novel signal covariation approaches have opened up a new avenue for non-invasive assessment of neural functional connectivity (FC) before birth. Early studies in this area have unearthed new insights about principles of prenatal brain function. However, very little is known about the emergence and maturation of neural networks during fetal life. Here, we obtained cross-sectional rs-fMRI data from 39 fetuses between 24 and 38 weeks postconceptual age to examine patterns of connectivity across ten neural FC networks. We identified primitive forms of motor, visual, default mode, thalamic, and temporal networks in the human fetal brain. We discovered the first evidence of increased long-range, cerebral-cerebellar, cortical-subcortical, and intra-hemispheric FC with advancing fetal age. Continued aggregation of data about fundamental neural connectivity systems in utero is essential to establishing principles of connectomics at the beginning of human life. Normative data provides a vital context against which to compare instances of abnormal neurobiological development.

The human brain undergoes dramatic maturational changes during late stages of fetal and early postnatal life. The importance of this period to the establishment of healthy neural connectivity is apparent in the high incidence of neural injury in preterm infants, in whom untimely exposure to ex-uterine factors interrupts neural connectivity. Though the relevance of this period to human neuroscience is apparent, little is known about functional neural networks in human fetal life. Here, we apply graph theoretical analysis to examine human fetal brain connectivity. Utilizing resting state functional magnetic resonance imaging (fMRI) data from 33 healthy human fetuses, 19 to 39 weeks gestational age (GA), our analyses reveal that the human fetal brain has modular organization and modules overlap functional systems observed postnatally. Age-related differences between younger (GA <31 weeks) and older (GA≥31 weeks) fetuses demonstrate that brain modularity decreases, and connectivity of the posterior cingulate to other brain networks becomes more negative, with advancing GA. By mimicking functional principles observed postnatally, these results support early emerging capacity for information processing in the human fetal brain. Current technical limitations, as well as the potential for fetal fMRI to one day produce major discoveries about fetal origins or antecedents of neural injury or disease are discussed.

Objectives To compare the accuracy of two-dimensional ultrasound (2D-US), three-dimensional ultrasound (3D-US) and magnetic resonance imaging (MRI) for the diagnosis of congenital anomalies without prior knowledge of indications and previous imaging findings. Methods This was a prospective, blinded case–control study comprising women with a singleton pregnancy with fetal congenital abnormalities identified on clinical ultrasound and those with an uncomplicated pregnancy. All women volunteered to undergo 2D-US, 3D-US and MRI, which were performed at one institution. Different examiners at a collaborating institution performed image interpretation. Sensitivity and specificity of the three imaging methods were calculated for individual anomalies, based on postnatal imaging and/or autopsy as the definitive diagnosis. Diagnostic confidence was graded on a four-point Likert scale. Results A total of 157 singleton pregnancies were enrolled, however nine cases were excluded owing to incomplete outcome, resulting in 148 fetuses (58 cases and 90 controls) included in the final analysis. Among cases, 13 (22.4%) had central nervous system (CNS) anomalies, 40 (69.0%) had non-CNS anomalies and five (8.6%) had both CNS and non-CNS anomalies. The main findings were: (1) MRI was more sensitive than 3D-US for diagnosing CNS anomalies (MRI, 88.9% (16/18) vs 3D-US, 66.7% (12/18) vs 2D-US, 72.2% (13/18); McNemar’s test for MRI vs 3D-US: P=0.046); (2) MRI provided additional information affecting prognosis and/or counseling in 22.2% (4/18) of fetuses with CNS anomalies; (3) 2D-US, 3D-US and MRI had similar sensitivity for diagnosing non-CNS anomalies; (4) specificity for all anomalies was highest for 3D-US (MRI, 85.6% (77/90) vs 3D-US, 94.4% (85/90) vs 2D-US, 92.2% (83/90); McNemar’s test for MRI vs 3D-US: P=0.03); and (5) the confidence of MRI for ruling out certain CNS abnormalities (usually questionable for cortical dysplasias or hemorrhage) that were not confirmed after delivery was lower than it was for 2D-US and 3D-US. Conclusions MRI was more sensitive than ultrasonography and provided additional information that changed prognosis, counseling or management in 22.2% of fetuses with CNS anomalies. False-positive diagnoses for subtle CNS findings were higher with MRI than with ultrasonography.