Dynamic macrostructural and microstructural changes take place from the mid-fetal stage to 2 years after birth. Delineating structural changes of the brain during early development provides new insights into the complicated processes of both typical development and the pathological mechanisms underlying various psychiatric and neurological disorders including autism, attention deficit hyperactivity disorder and schizophrenia. Decades of histological studies have identified strong spatial and functional maturation gradients in human brain gray and white matter. The recent improvements in magnetic resonance imaging (MRI) techniques, especially diffusion MRI (dMRI), relaxometry imaging, and magnetization transfer imaging (MTI) have provided unprecedented opportunities to non-invasively quantify and map the early developmental changes at whole brain and regional levels. Here, we review the recent advances in understanding early brain structural development during the second half of gestation and the first two postnatal years using modern MR techniques. Specifically, we review studies that delineate the emergence and microstructural maturation of white matter tracts, as well as dynamic mapping of inhomogeneous cortical microstructural organization unique to fetuses and infants. These imaging studies converge into maturational curves of MRI measurements that are distinctive across different white matter tracts and cortical regions. Furthermore, contemporary models offering biophysical interpretations of the dMRI-derived measurements are illustrated to infer the underlying microstructural changes. Collectively, this review summarizes findings that contribute to charting spatiotemporally heterogeneous gray and white matter structural development, offering MRI-based biomarkers of typical brain development and setting the stage for understanding aberrant brain development in neurodevelopmental disorders.

The brain is continuously modified by perceptual experience throughout life. Perceptual learning, which refers to the long-term performance improvement resulting from practice, has been widely used as a paradigm to study experience-dependent brain plasticity in adults [1, 2]. In the visual system, adult plasticity is largely believed to be restricted to the cortex, with subcortical structures losing their capacity for change after a critical period of development [3, 4]. Although various cortical mechanisms have been shown to mediate visual perceptual learning [5-12], there has been no reported investigation of perceptual learning in subcortical nuclei. Here, human subjects were trained on a contrast detection task for 30 days, leading to a significant contrast sensitivity improvement that was specific to the trained eye and the trained visual hemifield. Training also resulted in an eye- and hemifield-specific fMRI signal increase to low-contrast patterns in the magnocellular layers of the lateral geniculate nucleus (LGN), even when subjects did not pay attention to the patterns. Such an increase was absent in the parvocellular layers of the LGN and visual cortical areas. Furthermore, the behavioral benefit significantly correlated with the neural enhancement. These findings suggest that LGN signals can be amplified by training to detect faint patterns. Neural plasticity induced by perceptual learning in human adults might not be confined to the cortical level but might occur as early as at the thalamic level.

Comprehensive delineation of white matter (WM) microstructural maturation from birth to childhood is critical for understanding spatiotemporally differential circuit formation. Without a relatively large sample of datasets and coverage of critical developmental periods of both infancy and early childhood, differential maturational charts across WM tracts cannot be delineated. With diffusion tensor imaging (DTI) of 118 typically developing (TD) children aged 0–8 years and 31 children with autistic spectrum disorder (ASD) aged 2–7 years, the microstructure of every major WM tract and tract group was measured with DTI metrics to delineate differential WM maturation. The exponential model of microstructural maturation of all WM was identified. The WM developmental curves were separated into fast, intermediate, and slow phases in 0–8 years with distinctive time period of each phase across the tracts. Shorter periods of the fast and intermediate phases in certain tracts, such as the commissural tracts, indicated faster earlier development. With TD WM maturational curves as the reference, higher residual variance of WM microstructure was found in children with ASD. The presented comprehensive and differential charts of TD WM microstructural maturation of all major tracts and tract groups in 0–8 years provide reference standards for biomarker detection of neuropsychiatric disorders.

Human infancy is characterized by most rapid regional cerebral blood flow (rCBF) increases across lifespan and emergence of a fundamental brain system default-mode network (DMN). However, how infant rCBF changes spatiotemporally across the brain and how the rCBF increase supports emergence of functional networks such as DMN remains unknown. Here, by acquiring cutting-edge multi-modal MRI including pseudo-continuous arterial-spin-labeled perfusion MRI and resting-state functional MRI of 48 infants cross-sectionally, we elucidated unprecedented 4D spatiotemporal infant rCBF framework and region-specific physiology–function coupling across infancy. We found that faster rCBF increases in the DMN than visual and sensorimotor networks. We also found strongly coupled increases of rCBF and network strength specifically in the DMN, suggesting faster local blood flow increase to meet extraneuronal metabolic demands in the DMN maturation. These results offer insights into the physiological mechanism of brain functional network emergence and have important implications in altered network maturation in brain disorders.

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