Brain Development Neil Sonenklar, MD OBJECTIVES 1. Describe how the structure of the brain reflects evolutionary history 2. Understand how the brain grows at different rates 3. Know the basic cell types in the nervous system and their parts 4. Describe the processes of synaptogenesis, myelination and pruning 5. Describe how the above processes contribute to the plasticity of the brain 6. Know the sequence of how development of the brain correlates with sensory and motor development 7. List the sequence of myelogenetic cycles in language development and know the brain areas involved in language. 8. Describe how memory develops through infancy and how it correlates with developmental tasks Evolution of the brain The structure of the brain reflects evolutionary history. Reptiles, fish, amphibians have essentially brain-stem function (body functions heart rate, breathing, etc.) plus simple learning and stereotyped behaviors. These are governed by the oldest part of the brain the archicortex. (Figure 3). Above that is the paleomammalian cortex, present in primitive mammals. This surrounds the archicortex core. The components of this include the limbic system, cerebellum, and areas responsible for temperature regulation, and other bodily functions. The limbic system regulates emotional reactions which are much more complex in mammals than in insects, reptiles or birds. It is the also the area involved in disorders of emotion in humans. The other main component is the cerebellum. This controls coordination and fine motor control, for example tree-climbing abilities, balance of cats, manual dexterity in humans. The newest area, the neomammalian cortex consists of the thalamus and cerebral cortex. It surrounds the lower areas and is quite large with an intricately folded surface that increases its effective surface area in higher mammals (and dolphins). This area is responsible, in humans, for higher cognitive functions, flexible intelligence, and rational thought. In utero, the brain develops from the bottom up. (Figure 4)
Figure 1 Figure 2
Figure 3 From Fischer and Lazerson, 1984
Figure 3a
Figure 4 Brain growth Brain size in humans has increased relatively rapidly compared to other species. Bottlenosed dolphins (perhaps the most intelligent non-human creatures) have the same bodybrain ratio as humans. However, it took 15-20 million years to develop to this size compared to 3-4 million years for hominids. The brain is larger in proportion to our body size than other animals. (Ex. Human and sheep are around the same size but brain is 1/6 the size. Our brains should be about 400-550 grams but are around 1300 grams.) Brain growth is not steady. Most takes place before 4 ½ years. There is a spurt at around age 2 and again between 3 and 5. There is then a decrease in rate of growth between 5-6 years. The increase in brain size is related to changes in the organization and size of neurons rather than an increase in number. It is also due to an increase in supporting glial cells and myelination. Synaptogenesis, Myelination and pruning.
There are 2 basic cell types in the nervous system neurons and glial cells, including myelin. Neurons consist of 3 main parts; dendrites, which receive impulses from other neurons; cell body, responsible for cellular functions; and axons, which transmit impulses down the neuron to the next cell (Figure 5). Synapses are the connections between neurons. Most sensory and motor connections through spinal are established in utero. However, in the brain it is a bit different (Figure 6). Figure 5
Figure 6 There are at least 10 billion neurons in the brain and even more glial (nourishing and supporting) cells (Figure 7). The time between the 7th month in utero and age 2 is when there is the most intense growth and organization of synapses. At birth the brain weighs 25% of adult weight. At age 2 it has reached 75% of adult size. It is from increase in size of neurons, elaboration of myelin and glial cells, and increasing complexity of synaptic connections. Myelin provides insulation to help impulses move faster. The whole range of functioning, including sensory, motor, emotional, cognitive, language, is a result of the rapid synaptogenesis of the this period. This occurs when neurons connect by sending out (dendritic) axons. When it reaches the target neuron a connection, or synapse, is established that allows the impulse to move from one neuron to the next. As the impulse travels down the axon, neurons produce neurotransmitters which are released into the synaptic cleft and is then bound to a receptor protein on the dendrite of the next neuron or neurons, which then causes a chemical signal to propagate in the receptor neuron. This neurotransmission activates (or de-activates, in the case of inhibitory neurons) areas of the brain responsible for thoughts, emotions, internal regulation, and behavior. This arborization allows neurons to communicate in a coordinated way across multiple synapses and creates a system of control that mediates all aspects of behavior (Figure 8).
Figure 7
Figure 8 From Fischer and Lazerson As the connections are established, fatty myelin cells form around the axons insulating them like the coating on electrical wires. This allows more rapid transmission of impulses. The speed and efficiency increase through mid to late adolescence. As Myelination proceeds, new functions develop. At around age 1 the pyramidal tracts in the spinal cord become myelinated and this is when most infants start to walk. There is overproduction of synapses during the early growth period up to about age 2. Synaptic production is also influenced by use. Neurons that are frequently stimulated by transmission grow denser (dendritic) branches, which strengthen those connections. Those that are less used are gradually pruned throughout childhood and adolescence. Brain circuits are organized and specialized through pruning. This leads to the notion of critical periods for the development of some brain functions. If synaptic connections do not develop, pruning may cause some functions to be lost. In infants born with cataracts, if these are not removed by age 2, vision will not develop, even if the cataracts are removed later in life. Other functions are less influenced by such critical periods, for example, memory and learning. Synaptogenesis, Myelination and pruning occur at different rates in different brain areas.
Motor reflexes and sensory abilities (vision, hearing, etc.) are well developed at birth and rapidly mature during the first 6 months. Production of synapses in the visual and auditory cortices peak at around 3 months at which time pruning begins. Circuits guiding language comprehension and expression are overproduced until the end of the first year. Synaptic overproduction, myelination and pruning in the neocortex, which controls higher cognitive functions, continues through late adolescence. Plasticity Since, unlike other species where the brains are mature at birth, the human brain develops over many years and can be influenced by the quality of interactions with the environment. The brains of young children show much plasticity in the ability to develop new pathways. Children who suffer brain injury before the age of 5 can recover full function because new circuits can develop. A child who suffers injury to the left cerebral cortex (usually the site of language function) can compensate by shifting that function to the right hemisphere. Positive influences (touching, playing, interacting) support brain development. But because of the plasticity and pruning the brain is vulnerable to neglect, trauma, and malnutrition. In orphanages where infants spend most of the time alone in their cribs with minimal interaction with adult caretakers the babies show significant motor delays. They do not receive the sensory input from skin and muscles or the emotional contact. For these deprived infants, even small increases in stimulation (holding, playing) (15 hours of stimulation in a 1 month period, in one study) greatly increased the developmental maturity of 1 year olds. So can parents make their kids smarter by providing more stimulation? In another study from the sixties, it was found that babies that had moderate levels of stimulation (1 or 2 toys within their reach) showed immediate interest in their environment compared to both infants who were deprived of toys and those with too much stimulation (many mobiles, toys, pictures). The latter infants seemed overwhelmed by the amount of stimulation, tended to ignore it and cried a great deal. Infancy Most species are out and ready to function soon after birth. Humans take a while longer largely related to the development of the cerebral cortex. This is most evident in the first 2 years. This increase in brain size is largely because of increase in the size of the neurons and the density of the connections, as well as supporting glial cells and Myelination. In the cortex, there are 2 patterns of development for sensory and motor functions. In the first 3 months the greatest development in the motor cortex is in areas controlling the head, upper trunk and arms. Between 3 months and 1 year the areas controlling the legs and hands show the most development. The sensory cortex shows the same sequence but lag behind motor development until about age 2 when it catches up. Sensorimotor skills follow these developments. The association areas show major
development between 6 months and 2 years as the child shows more complex capabilities. We are still learning about the specific functions of the association areas but it is know that they combine information from the sensory and motor areas and are essential in the elaboration of higher cognitive functions such as anticipation and reasoning which we see in things like imitation and object constancy. An example is potty training. Babies can be conditioned to empty their bladders when placed on a potty but voluntary control does not occur until 15 18 months (can be as late as 3 years). The areas of the cortex corresponding to bladder emptying develop sooner than those for voluntary control. The sensory neural pathway between the bladder and cortex must be able to transmit the signal that the bladder is full, and the nervous system must have be able to have that signal take precedence over the brain s other activities (such as involvement in an interesting game). Finally the child must be able to associate this signal with the need to get to the potty. School age At around age 6 children enter the concrete operations stage of development. Although there are changes in brain size and function accompanying every cognitive advance, those that happen at this time are well documented. This is called the 5 to 7 shift. We have already mentioned the increase myelination. There is also a change in electrical activity. There is a sharp increase to higher (more mature) frequency. There is also a change in visual evoked potentials. The magnitude of this response increases until around 6 then slowly drops to adult level (there is a small peak in the teens, which may correspond to the change to formal operational ability). In certain conditions, such as PKU, children must be on a special diet low in phenylalanine to avoid brain damage and mental retardation. However, after age 6 this is no longer necessary. Also, febrile seizures seem to stop around age 6 in children who have had them when younger. Adolescence The timing of changes in adolescent thinking specifically in relation to puberty is unclear. There seem to be 2 periods of rapid change one at the beginning (10-12 year) and one at the end (14-16) of puberty. There are spurts in brain development that correspond to the changes in thinking process. At both 10-12 and again at 14-16 there is high rate of growth and dramatic spurts in brain wave activity. There is the sense that this change in brain organization makes the switch to formal operations possible. Researchers have tried to correlate changes in brain development with Piagetian periods, specifically using head growth. The idea is that children might learn skills better at these periods. Although there is evidence that there are brain changes in spurts with Piagetian changes and that some individual children grow in spurts and these correlate with the start of a new Piagetian period, there is only a broad non-specific correlation between brain development and Piagetian periods. There is no support for the notion that children do not learn as well when their brains are growing slowly
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Figure 10 Language development There are periods of rapidly increasing myelin formation in particular brain systems. Three are important in language development. These are called the Myelogenetic cycles (Figure 11). The first (in the primitive brain (archicortex) and limbic system) starts before birth and ends in early infancy. It may be associated with the development of babbling. The second is in the higher brain regions, begins around birth and continues
until 3½ to 4½ and is associated with speech development in infancy and preschool years. The third cycle is in the association areas of the cortex and is related to intelligence and memory. Myelination in these areas begins at birth and is not completed until late adolescence (recent court cases have used some of this research in their decisions regarding culpability in adolescents focusing on diminished capacity as a result of agerelated immaturity). Some association areas are particularly important for speech development. Broca s area is located on left frontal lobe adjacent to the part of the motor cortex that controls lips, tongue, soft palate and vocal cords and coordinates those areas in speech. Wernicke s area in the left temporal lobe (between Heschl s gyrus receiver of auditory stimuli and the angular gyrus - way station between visual (occipital) and auditory regions). Damage in these areas results in significant language impairment. Damage in Broca s area results in slow, labored speech (as in stroke victims). Damage in Wernicke s area results in fluent speech with minimal content and poor comprehension (common in severe alcoholics). The arcuate fasciculus is a nerve bundle that joins these areas. When this is damaged, speech is fluent but abnormal; and the patient can understand words but not repeat them. Figure 11 Fischer and Lazerson, 1984
Infancy There is evidence that infants are very sensitive to speech sounds. Newborns can differentiate prose passages from those they have heard in the womb in the last 6 weeks of pregnancy. They can also distinguish between phonetic contrasts they have never heard. For example, a 6 month old Japanese child can distinguish /r/ from /l/ - a difference that does not change meaning in Japanese. By 12 months they are like adults who do not distinguish those sounds. 3 month olds can distinguish the full range of human language sounds.. By age 1 sound recognition has become increasingly restricted to those in the language the child hears. They tend to assimilate unfamiliar sounds with those they know (the /r/ and /l/ in Japanese) instead of the contrast. New sound recognition can occur until middle childhood. This is why children up to the age of 10 or so can learn new languages without accents. There may be a sensitive period for acquiring language between ages 1 and 2, peaking in later preschool years. It continues to some degree until 13-15 years. Wild children who were raised in isolation provide a natural experiment in language deprivation. Usually, these children have only been able to learn a few words. Memory Certain kinds of memory in humans are associated with preserved components of each of these evolutionary brain regions. The archicortex would relate to autonomic processes. The Paleomammalian cortex is related to certain procedural patterning. This might include functions such as nursing, mothering, early sensorimotor and play patterns. The neomammalian cortex gives rise to complex memory functions, association and language. Perception, attention, pattern recognition, filtering, selective information coding and retrieval are all memory components. Memory, like other functions, develops in spurts related to CNS maturation. For infants, memory is short a one month old can remember a mobile for about 24 hrs. A 6 month old can recall an object seen for a few minutes for up to several weeks. Memory increases in duration as the memories accumulate and memory becomes less dependent on context. Stranger anxiety, object permanence and attachment behaviors are evidence of this. Memories of past experiences gradually lead to the ability to anticipate future events. For example, the baby can tell the mother is getting ready to leave by observing her preparations. Memory storage is an active process, not just warehousing. Short-term memory allows the recall at about 30 seconds of 5 to 9 perceived objects, assuming the child pays attention and registers them. Short-term items may be encoded into long-term memory. You might find that repetition and practicing helps you remember things later. Parietal lobe, thalamus and midbrain must be functioning for pattern recognition. Occipital lobe is where visual word forms are developed. Left hemisphere is better than
the right for mental imagery and arranging shapes. Semantic language tasks are processed in the left anterior frontal lobe. Auditory word forms are processed in the left tempoparietal cortex. Auditory memory and attention (tasks such as digit span recall) involve the left supramarginal and angular gyri. With maturation the child develops more efficient strategies for episodic memory. This is automatic storage and retrieval of personal experiences that are located spatially and ordered in time. Kids from 4 6 can locate events with respect to where they happened but are not very good at recalling the date or time. By age 10, they have developed the concept of historical time and can order events temporally. In general, children short-term memories are as good or better than adults for things they understand. However, they are easily prone to suggestion, which can affect the accuracy of their recall (hence the controversies around child testimony in court). Children notice things that might be considered irrelevant by adults but they make more errors of omission. They fill gaps in their memory by making things up. Since they lack previous knowledge they may have trouble relating events and organizing disparate elements into a cohesive whole. Piaget noted that we reconstruct the past as a function of the present and that there may be no such thing as pure memories. All memories of childhood may be created from later events interwoven with fantasy. Figure 12