Genetic expression behind the development of our brains is most active before birth, in the early months of pregnancy, and during our teenage years, scientists have found.

There is a quieter intervening “movement” in the three-part “symphony” of human brain development, but one that is more sensitive to environmental factors, say the researchers publishing in the journal Neuron.

The initial surge of brain-developing genetic expression takes place during the first two-thirds of our gestation in the uterus, says the team led from the Yale School of Medicine in New Haven, CT.

The middle intermission then lasts from the final trimester of pregnancy until adolescence, at which point the genetic activity surges again for the final phase of our brain’s development.

These two most active spurts relevant to human brain power, found to sandwich the childhood years, involve the development of the cerebral neocortex:

  • In which general architecture is created during the first 3 months of fetal development after conception, and
  • More subtle shaping and specialization of the structure occurs during the teenage years.
What is the cerebral neocortex?

The cerebral neocortex is the area of the brain governing perception, behavior and cognition.

It is unique to mammals, and the newest addition to our brain – “considered to be the crowning achievement of evolution and the biological substrate of human mental prowess,” writes leading neurologist and neuroscientist Dr. Pasko Rakic, also from Yale.1

Our highly developed cerebral neocortex is what makes us human.

Prof. Rakic continues: “If any organ of our body should be substantially different from any other species, it is the cerebral neocortex, the center of extraordinary human cognitive abilities.”

While the neocortical development, as dictated by genes, is most active before birth and again in the teenage years, the genetically less active middle part of our brain development is important formatively, says the senior study author.

Nenad Sestan, professor of neurobiology at Yale’s Kavli Institute for Neuroscience, says:

“The findings emphasize the importance of the proper interplay between genes and environment in the child’s earliest years after birth, when the formation of synaptic connections between brain cells becomes synchronized, which shape how brain structures will be used later in life.”

The scientists analyzed gene expression in the human and macaque monkey neocortex for the study, which they set up because genetic events leading to the development of the human cerebral neocortex “are poorly understood.”

For the three phases identified – forming an “hourglass” shape of developmental activity through time – the following observations were made:

  1. The first phase, corresponding to prenatal development, was characterized by the highest number of differential expressed genes
  2. The second, pre-adolescent phase, showed fewer gene expression differences and more synchronization between developing areas, and
  3. The third phase, from adolescence onward, saw another rise in differential gene expression, in certain predominant areas.

The researchers were “intrigued” to find that some of the patterns of genetic activity making up the human hourglass sketch were not observed in the developing monkeys.

This suggests the activity may play a role in shaping uniquely human brain development, they say.

The “global symmetry” to the findings makes them applicable to the population level, the authors add. And the findings relating to the middle phase, explains Prof. Sestan, emphasize the sensitivity of children’s earliest years after birth.

This is a time when the process of forming nerve connections shapes how brain structures will be used later in life, Prof. Sestan says. He points out:

“For instance, disruptions in synchronization of synaptic connections during a child’s earliest years have been implicated in autism.”

Using language from architectural town planning, Prof. Sestan says that while the first, most active phase of brain development creates the basic structure of the “neighborhood” of the human brain, it is better defined by the “community” living within it, developed more slowly during the childhood phase.

“The neighborhoods get built quickly and then everything slows down and the neocortex focuses solely on developing connections, almost like an electrical grid,” he adds.

The third phase can be compared to identities developing in geographical places, Prof. Sestan says:

“Later, when these regions are synchronized, the neighborhoods begin to take on distinct functional identities, like Little Italy or Chinatown.”