24th November 2023

Foetal Development 

The period of foetal development spans from week 9 of gestation until term.

Migration

During weeks 12 to 20, vast numbers of proliferated neurons migrate from the ventricular and subventricular zones to different areas of the growing cortex. The earliest neurons may migrate short distances via somal translocation, extending long processes and rearranging intracellular structures to ‘reach’ their target destination. However, migration mostly proceeds along scaffolding structures provided by glial (supporting) cells.

The earliest neurons to migrate generally constitute the deepest layers of the forming cortex, with later neurons forming more superficial layers. Four transient layers of neurons are initially formed – the preplate, marginal zone, subplate and cortical plate. The subplate and cortical plate are of particular importance: migrating neurons will initially synapse with subplate neurons, where they receive connections from neurons in immature thalamic and brainstem areas but later form permanent synapses with cortical plate neurons and break away from the subplate. The redundant subplate eventually degenerates, whilst the cortical plate gives rise to layers I-VI of the neocortex.

Structural MRI (sMRI) has been used to confirm such migration events. You will recall that sMRI utilises a large magnet and radiofrequency pulses to influence the natural magnetic properties of protons in tissues in order to create detailed anatomical images. T1 sequences enhance fat signal, whereas T2 sequences enhance water signal. When applied to the examination of the foetus, sMRI is sometimes simply known as ‘foetal MRI’.

By week 20, foetal MRI can distinguish the cortical plate (low T2 signal) from subplate (high T2 signal). Studies show that the subplate is at its thickest (approximately four-times that of the cortical plate) at week 22. After week 30, however, the subplate gradually disappears, with accompanying reductions in proliferative zone volumes on MRI. The cortical plate grows; meanwhile, driving increases in cortical thickness. Helpfully, one research group recently published a full ‘spatiotemporal atlas’ of brain changes between gestational weeks 21 and 39, available to view online (see Gholipour et al. 2017, Scientific Reports).

Myelination

During myelination, oligodendrocytes and Schwann cells ensheath central and peripheral nervous system axons, respectively, with fatty myelin. The primary function of the myelin sheath is to speed up the axonal propagation of action potentials via saltatory conduction.

Myelination begins by the fifth month of gestation and is mostly complete by the second year of life but continues into the third decade of life in some areas (e.g. corpus callosum). Myelination begins in the spinal cord / at exiting motor roots and progresses rostrally. Sensory pathways generally myelinate earlier than motor pathways, and association areas myelinate last. Some fibres will never undergo myelination.

Again, much of what is known about myelination comes from non-human and post-mortem human histology. That said, diffusion tensor imaging (DTI) – an MRI technique useful for the assessment of white matter microstructure – has been used to study myelination as early as 18 weeks gestation. Within DTI, fractional anisotropy (FA) describes the extent to which water molecules diffuse along axons (versus freely in all directions), where FA values (between 0 and 1) are directly proportional to axon/tract density. DTI (by FA) studies in foetuses aged >23 weeks corroborate that myelination likely begins in corticospinal tracts before progressing to the optic radiations and corpus callosum. Neurite orientation dispersion and density imaging (NODDI) is a diffusion MR technique specifically developed for brain MRI and may image human neurodevelopment with greater sensitivity than standard DTI.