The cerebral cortex begins forming around week 5 of gestation, when the first neurons are generated in the developing brain. But “development” is not a single event. The cortex goes through a series of overlapping stages spanning most of pregnancy, from the birth of its earliest cells through the formation of its signature folds, with some processes continuing well after birth.
Weeks 5 Through 8: The First Neurons Appear
At gestational week 5, progenitor cells lining the brain’s inner surface begin dividing in a new way. Instead of simply copying themselves, they start producing two different daughter cells: one stays behind as a progenitor, and the other becomes either a neuron or an intermediate cell that will produce more neurons. This shift marks the onset of neurogenesis, the process of building the brain’s cellular workforce.
By weeks 7 to 8, these newly born neurons have migrated outward to form the cortical plate, the structure that will eventually become the six-layered cortex found in adults. The cortical plate forms when it splits an earlier temporary layer (called the preplate) into two, essentially inserting itself between them. This is the first recognizable precursor of the cerebral cortex as a distinct structure.
Weeks 8 Through 20: Building Layers From the Inside Out
Once the cortical plate appears, the cortex builds itself in an inside-out fashion. Neurons born earliest settle into the deepest layers, while neurons born later climb past them to occupy progressively outer layers. Each neuron travels along the long fibers of specialized guide cells called radial glia, which stretch from the brain’s inner surface to its outer edge like scaffolding.
During the early part of this period (roughly weeks 8 through 12), a temporary zone called the subplate forms just beneath the cortical plate. The subplate acts as a waiting room and routing station: incoming connections from other brain regions park here before being directed to their final targets in the cortex above. This transient zone is at its most prominent during the second half of pregnancy and doesn’t fully dissolve until about three months after birth in primary brain areas, and even later in higher-order regions responsible for complex thinking.
By around week 12, the distance between where neurons are born and where they need to end up has grown so large that migrating cells can no longer simply extend a process all the way to the brain’s outer surface. Instead, they rely more heavily on the radial glia scaffolding and adopt a more complex, multi-step migration pattern to reach the cortical plate.
Weeks 14 Through 24: Folding, Synapses, and First Signals
Around week 14, the brain’s surface begins developing its first major folds, called primary sulci. Before this point the cortex is relatively smooth. The earliest fold to appear is the Sylvian fissure, the deep groove that separates the temporal lobe from the frontal and parietal lobes. These folds dramatically increase the cortex’s surface area, allowing far more neural tissue to fit inside the skull.
Synapses, the junctions where neurons communicate with each other, begin proliferating around week 20. The hippocampus (a region critical for memory) shows abundant synapses even earlier, by weeks 15 to 16. But in the cortex itself, week 20 marks the start of a synapse-building process that will accelerate through the third trimester and peak during the first two years of life.
Also around weeks 20 to 21, neurons in the subplate zone begin generating spontaneous electrical activity. Researchers recording from human fetal brain tissue at this age have detected bursts of action potentials riding on top of sustained electrical waves. These early signals occur roughly four months before birth and are thought to help organize the developing circuitry, even before the cortex is receiving meaningful sensory input from the outside world.
Week 24: Sensory Pathways Reach the Cortex
A major milestone arrives around week 24, when nerve fibers carrying sensory information from the thalamus (the brain’s relay center) begin connecting directly to the cortical plate. Before this point, those fibers have been waiting in the subplate zone below. Their arrival in the cortex itself means that, for the first time, sensory signals have a direct pathway to the brain region that will eventually process them into conscious experience. This connection forms first in areas handling basic senses like touch and vision, and later in the association areas responsible for more complex processing.
Weeks 28 Through Birth: Rapid Folding and Growth
The third trimester is a period of explosive cortical growth. Secondary sulci, the smaller folds that branch off from the primary ones, appear starting around week 32. Tertiary sulci, the finest grooves that give each brain its unique fingerprint-like pattern, don’t emerge until around week 39, near full term. This means the brain’s folding pattern is still actively forming right up to birth.
Synapse formation accelerates dramatically during this period, driven by a burst of dendritic growth. Dendrites are the branch-like extensions neurons use to receive signals from other cells, and as they sprout and multiply, the number of possible connections between neurons skyrockets. The connections being wired between the cortex’s deeper layers and its incoming sensory pathways are also maturing, replacing the temporary subplate circuits with more permanent ones.
The cortex itself is thickening and expanding in surface area throughout this time. The brain roughly doubles in volume during the final ten weeks of pregnancy, and much of that growth comes from the cortex and its underlying white matter tracts.
Development Continues After Birth
Birth does not mark the end of cortical development. The subplate zone in primary sensory and motor areas dissolves by about three months after birth, while in association cortices it persists through the remainder of the first year. Synapse numbers continue climbing steeply, peaking during the first two years of life before the brain begins pruning excess connections. The six-layered structure of the cortex is in place well before birth, but the fine-tuning of its circuits is a postnatal process that extends through childhood.
Nutrients That Shape Cortical Development
Certain nutrients play outsized roles during the weeks when the cortex is forming its layers. Choline is one of the most important. It supports cell membrane formation and influences gene expression during brain development. In animal studies, low choline availability during the period of active cortical building reduced the pool of neural progenitor cells, increased cell death in the cortex, and disrupted the normal layering pattern by altering the proportions of early-born and late-born neurons.
Folate and methionine work alongside choline as methyl donors, molecules that help regulate which genes are turned on or off during development. Their metabolic pathways overlap, and while a choline-rich diet can partially compensate for folate deficiency, each nutrient plays a role the others cannot fully replace. These nutrients matter most during the first and second trimesters, when the cortex is generating its neurons, building its layers, and establishing its earliest connections.