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The Central Nervous System (CNS), which consists of the brain and spinal cord, is in charge of how our bodies function. The CNS takes in, interprets and sends out signals. How our brains develop is an amazing story. This is an overview of some of the main structures and events in the development of our Central Nervous System.
Brain development is determined by
1. Genes
2. Environment
Half of a child's genes come from the father and half from the mother. Genes direct how the brain grows. The environment includes the conditions within the womb, what happens during delivery, and the conditions and events each day after birth (both physical and emotional). Usually the genes a child gets from each parent are adequate for good brain development. A normal full-term, healthy pregnancy provides the best environment to support good early brain development.
We hope the information you find here will add to your understanding of how the brain develops, some of its functions and how this may relate to your premature infant's development. Learning more about the brain can be useful in making sense of reports on brain imaging or help in discussions with your children's doctors. As you read this material you will be introduced to many new terms. Some of them may seem very foreign to you. Do not be put off by the words, we will try to make them understandable. (Click on any highlighted word for a definition.)
Maturation of the Central Nervous System
The maturation of the Central Nervous System can be divided into six, sequential, major events. These events will be talked about as separate stages. However, in real time there is overlap, with several stages being in the process of starting or stopping at any given time. It is a very exciting and active process. Understanding of this process is still evolving.
Six Stages of CNS Maturation
Dorsal Induction
Ventral Induction
Proliferation
Migration
Organization
Myelination
Dorsal induction takes place from 18 to 26 days of gestation. On day 18 the developing embryo (still only a small clump of cells) folds back on itself to form what is called the "neural tube." The neural tube will eventually develop into the brain and the spinal cord. During this phase there is further folding, thickening and stretching out of the neural tube. On day 26 the neural tube closes and this marks the end of dorsal induction. The origins of the entire CNS has been laid down. If for any reason something happened to slow down or stop this phase it would usually result in a miscarriage. In rare instances the pregnancy may continue, but there would be a profound impairment (for example, meningomyelocele or anacephaly).
Ventral Induction takes place from 4 to 10 weeks of gestation. This is the second stage of CNS development. This stage involves the head end of the embryo and the developing neural tube that will eventually form the face and brain. A number of brain structures are formed during this phase.
- The major portion of the brain, the cerebrum, develops during this second stage of CNS development. The cerebrum has two parts: the outer layer ("cerebral cortex") and the inner layer ("cerebral medulla"). The cerebrum is the structure most of us picture when we think about what a brain looks like. The cerebral cortex is referred to as "gray matter." It is called gray matter because it is darker in color that the layer underneath. Early anatomists thought the dark layer reminded them of tree bark and chose the word "cortex" (Latin for "bark"). The gray matter is made up of densely packed nerve cell bodies, which give it its gray color. Under the gray matter is the cerebral medulla, which is referred to as "white matter." White matter is made up of myelinated axons, and it is the white myelin that gives the white matter its color.
- A series of cleavages divides the cerebrum into two halves known as the right and left hemispheres. The division also involves the hypothalamus and the thalamus. The brain structures, which process vision and smell, are paired within these two hemispheres. The left hemisphere eventually becomes the main location for processing speech and language in most children. In general, the left hemisphere performs mathematical, analytical, and verbal functions. The right hemisphere processes visual, spatial and musical information. Each half of the cerebrum controls the opposite side of the body. Sensations and control signals communicate back and forth from the left side of the body to the right hemisphere. Sensations and control signals from the right side of the body communicate with the left hemisphere.
- The brainstem consists of all portions of the brain except the cerebrum and cerebellum. It connects the brain and the spinal cord. The brain stem regulates life-sustaining mechanisms such as breathing, heart rate, and vasomotor functions. It is also part of the mechanism for arousal, wakefulness, and alertness. The brain stem serves to relay impulses back and forth between the spinal column and the upper parts of the brain.
- Another structure that arises during ventral induction is the cerebellum, a small structure located at the rear of the brain. The cerebellum will eventually play a role in coordinating smooth motor movements, including speech articulation.
- Approximately half of the end of the neural tube ultimately forms the spinal cord. The spinal cord is laid out in repeated segments, from the base of the skull all the way down our backs. Nerves move out from the spinal cord throughout the body. This is referred to as sensory motor innervation. The center of the neural tube is hollow and the upper end will eventually form the ventricles of the brain and the central canal of the spinal cord.
If anything happens to slow down or stop this phase of brain development, a miscarriage typically results. If the pregnancy continued, the disruption might end in the brain making abnormal cleavages or cysts separating the cerebral hemispheres. These events would result in profound impairments.
Proliferation is the third stage of CNS development. Proliferation is a two-phase process consisting of neuroblasts and glioblasts. Neuroblasts are cells that will develop into nerve cells. Glioblasts are cells that will form the basic support structures in the mature brain. The first phase, neuroblasts, goes through its most rapid proliferation from 2 to 4 months of gestation. The second phase, glioblasts, is also occurring from 2 to 4 months of gestation, but it goes through its most rapid proliferation from roughly 5 to 12 months postnatally. Both neuroblasts and glioblasts begin to grow rapidly during proliferation, dividing and multiplying to create the number of nerve cells a person will have for life, approximately 100 billion. This activity occurs at the future site of the ventricular system.
The most basic unit of the CNS is the nerve cell or "neuron." The neuron underlies all human behavior. The number of neurons created during the proliferation stage is 40-50 percent more cells than needed for a functioning mature brain. Once proliferation stops, the neurons become irreplaceable. We do not make new neurons. However, some later reorganization of the function of some neurons, can occur. For example, when a stroke causes neurons to die, it is possible for other neurons to take over the dead cells' functions and some recovery of movement or speech to occur. The function will not usually be as smooth and well coordinated as the original.
If there is any interruption of the third stage of CNS development, the brain may never reach its full growth potential. If this were to occur an abnormally small brain size for the body (2 to 3 standard deviations below average) usually results. This condition is called microcephaly and is usually associated with mild to moderate mental retardation.
Migration begins at 6 to 8 weeks of gestation through 8 months gestation. This is the movement of nerve cells from the proliferation zone (at the future site of the ventricular system) to their final position somewhere in the CNS. The movement of cells is thought to occur along migrational pathways, different groups of cells going in different locations. For example, some cell will move to the outer surface of the cerebrum, forming the 3-mm-thick cerebral cortex (remember this from the second stage - ventral induction).
- The cerebral cortex contains 6 layers of cells. Migration begins with the innermost layer (layer 6 - this layer is present by week 8 of gestation) and subsequently progresses towards the outermost layer (layer 1 - present by the 8th month of gestation). The layers of the cerebral cortex are designed to either receive or send information. For instance, cortical layer 5 is designed for control of body movement (sending motor commands) while layer 4 takes in information from the senses.
- To complicate matters further the cerebral cortex is not only organized in layers (horizontally) but it is also organized in columns (vertically). Cells within a column will share a functional feature that is different from the functions of the cells in the column next to it. The glial cells, we were introduced to under the third stage of the CNS development (proliferation), are the cells that guide the neurons to a specific area. Glial cells are also called "glue" cells and provide supportive structure during a series of changes. Eventually, information from cells within distinct layers and columns of the cerebral cortex are received, processed, transformed and then sent out to other areas of the brain.
- The process of migration can be thought of as an automated conveyer belt. First, a cell changes from a neuroblast to a neuron and becomes aligned to a radical glial cell. Second, the neuron cell propels itself along the surface of the glial cell. When it reaches its destination, the neuron is detached from the glial cell.
- During the process of migration, some groups of cells migrate to form elevations (gyri) and some form groove-like depressions (sulci) that evolve into the familiar hill and valley appearance you have seen in pictures of the brain. The hills and valleys are referred to as convolutions. The hill and valley configuration of the brain functions to greatly increase the surface area of the cerebrum. This allows the large number of neurons contained in the cerebrum to fit within the skull.
- Another group of migrating cell creates the corpus callosum, a "bridge" that connects the two cerebral hemispheres. The corpus callosum makes it possible for information to be communicated between the right and left hemispheres.
- The cerebral cortex, with its six layers, is divided into lobes. The lobes generally relate to the skull bones that cover them: frontal, parietal, temporal and occipital. The exception is the limbic lobe, which incorporates part of three of the other lobes (frontal, temporal and parietal). The current thinking about the functions of the different lobes is as follows:
Frontal lobe (behind the forehead) concerned with intellectual functions such as reasoning and abstract thinking, aggression, sexual behavior, smell, voluntary movement and articulation of speech.
Parietal lobe (upper right and left sides of the head) concerned with body sensory awareness (including taste), the use of symbols for communication (language), abstract reasoning (math) and body imaging.
Temporal lobe (on the right and left side of the head, above and behind the ears) part of this lobe is limbic and is concerned with the formations of emotion (love, anger, aggression, compulsion and sexual behavior). The non-limbic portion of the lobe is concerned with the interpretation of language, awareness and discrimination of sound (hearing: auditory area), and constitutes a major memory processing area.
Occipital lobe (the back of the head) concerned with receiving, interpreting and discriminating visual stimuli from the optic tract, and association of those visual impulses with other cortical areas (e.g. memory).
If there is a major disruption in the migration of neurons, the results include abnormal brain gyral patterns and collections of neurons in abnormal locations (called heterotopias). These are generally rare disorders.
Children who are born prematurely are delivered during the later part of the migration period. Children who sustain brain injury during this period (for example, SEH - subependimal hemorrhage or PVL - periventricular leukomalacia) can have disorders or late migration. With these conditions there is a disruption of the radical glial fibers that then pull back from the cortical surface. If you remember from our discussion above, the neurons can only go where the glial cells guide them. When a disruption in the "conveyor belt" occurs, the neurons become stranded. Some researchers feel that disorders of late migration may contribute to the impaired coordination, visual perceptual problems, and seizures experienced by many children born prematurely who do not show evidence of other brain injury.
Organization begins at 6 months of gestation and continues well after birth. This is the fifth stage of CNS development. Once formed and in place, neurons begin to sprout branches referred to as axons and dendrites. At this stage most neurons consist of three parts:
- a cell body
- axons - nerve fibers that send signals away from the cell body to other neurons. Neurons usually only have one axon.
- dendrites - a number of short tree-like branches that receive signals from other neurons. A neuron can have hundreds of dendrites.
Once the axons and dendrites are formed they begin to communicate. The process is something like a relay race. The communication that transmits a message between the axon of a sending neuron and the dendrite of a receiving neuron is called a synapse. The synapse permits the conduction of electrochemical impulses among a large number of neurons almost simultaneously.
Initially, there are more synapses created than are needed; however, only those used will survive. Just as we prune a tree that is overgrown, the brain "prunes" away synapses that are not used. This process is a way of fine tuning the maturing CNS. Just like with neurons, the brain starts out creating more synapses than it will ever need. Over time (and into the teen years) those cells that are not needed will die off. It is important to note that the brain is not rigid and inflexible even after the teen years. Recent thought on this process is that there is still some neuronal flexibility in response to experience throughout the life course. Adults can still make new synaptic connections for novel learning experiences.
Myelination begins at 6 months of gestation and continues into adulthood. This is the sixth and final stage of CNS development. The glial cells (those support cells that are part of the "conveyor belt") produce myelin. Myelin is a fatty covering that eventually coats and insulates many axons to provide for rapid impulse transmission. The cerebrum has both an outer layer (the "cerebral cortex") and an inner layer (the "cerebral medulla"). The cerebral medulla contains many bundles of myelinated axons which give it a white appearance (hence the name "white matter"). The myelinated axons fire more rapidly and efficiently than non-myelinated fibers. True maturity of the CNS only occurs after the Myelination process has fully developed.
Definitions:
Genes (nature)/environment (nurture) are the two main components of the ongoing debate over whether genetic endowment or environmental nurturing are more important. The "nature/nurture debate" asks "Which is more important genes (nature) or environment (nurture)?" The relative importance of each helps determine how well the brain can recover from injury or lack of stimulation early in life. In the literature review article, "Change and the Continuity on Neurobehavioral Development: Lessons from the Study of Neurobiology and Neural Plasticity," published in the journal Infant Behavior and Development (vol. 22, no. 4, 1999, pg.415), Charles A Nelson tried to address these questions. He concluded ".that the events that transpire to mold and sculpt the brain are (a) not always limited to the first years of life and (b) are activity-dependent. As a result, we need to be careful in assuming blindly that the first few years of life are a critical period in general: rather, it is perhaps wisest to view these years as a critical period for some functions, a sensitive period for others, and broadly tuned and receptive to modification for the duration of the life span for still others. Finally, because so many aspects of development are activity-dependent, we should not be surprised to observe a broad range of individual differences: after all, given differences in prenatal histories, in genomes, in rearing environments in caretaking, and in inculturation, to name just a few, each brain is left to incorporate experiences differently. This is turn, will result in differences in how infants embrace their environments, which in turn will lead to further differences in neural substrate.ad infinitum."
Dorsal refers to the back of something. A structure is called "dorsal" if it is more towards the back than another structure.
Induction refers to the act or process of causing something to happen. When induction is used in talking about early development of the embryo it refers to the stimulating and directing effect shown by certain tissues on neighboring tissues or body parts.
Gestation refers to the time from fertilization (joining of the egg and the sperm) until birth. Full-term gestation is a 40 week process.
Meningomyelocele is the failure of the closing of the neural tube resulting in a defect where part of the spinal cord herniates (protrudes) out along the spinal column.
Anencephaly is a condition where major parts of the brain are completely missing or reduced to small masses attached to the base of the skull. This condition is usually incompatible with life.
Ventral refers to a structure being more in front than another structure of the body or more toward the belly surface.
Hypothalamus is an important structure located in the lower part of the sidewall of the 3rd ventricle. It exerts control over a number of body functions such as water balance, body temperature, hunger and sleep.
Thalamus is a brain structure located on the lateral wall of the 3rd ventricle. It is the main relay center for sensory impulses to the cerebral cortex. It produces conscious recognition of pain, temperature, and touch. It plays a part in the mechanism responsible for emotion by associating sensory impulses with feelings of pleasantness and unpleasantness.
Innervation refers to the distribution or supply or nerves to a part of the body.
Ventricles or the Ventricular System involves four reservoirs positioned in the brain. The lining of these reservoirs is highly vascular tissue that secretes cerebrospinal fluid (CSF). This is a clear fluid that circulates around the brain and spinal column. It is constantly being produced and reabsorbed in a continuous flow from one ventricle to the next and down the spinal cord. The CSF has a shock-absorbing function of great significance to the brain and spinal cord. The CNS literally floats in CFS. Blockage in the ventricular system can lead to a build up of CSF in one or more ventricles, a condition called hydrocephalus. If untreated, the build up of pressure caused by the blockage can cause significant brain damage. Hydrocephalus can be treated by placement of a tube(s) into the ventricle(s) to drain the excess CSF. This is commonly referred to as a "shunt." In some instances hydrocephalus will stop on its own and will not require shunting.
