The Brain Is the Ultimate Organ of Adaptation

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CHAPTER 64

THE DEVELOPING BRAIN

Draft: 2-25-2000

The brain is the ultimate organ of adaptation. It takes in information and orchestrates complex behavioral repertoires that allow us to act in sometimes marvelous, sometimes terrible ways. For humans, most of what we think of as the “self” –what we think, what we remember, what we can do, how we feel--is acquired by the brain from the experiences we have after birth. Some of this information is acquired during critical or sensitive periods of development when the brain appears uniquely ready to take in certain kinds of information, while other information can be acquired across broad swaths of development that can extend into adulthood. This spectrum of possibilities is well captured by coinciding evidence of the remarkably rapid brain development that characterizes early development and of the brain’s lifelong capacity for growth and change. The balance between the enduring significance of early brain development and the impressive plasticity of the brain lies at the heart of the current controversy about the effects on the brain of early experience on the brain.

The past 20 years have seen unprecedented progress in our understanding of how the brain develops and, in particular, of the phenomenal changes in both the circuitry and neurochemistry of the brain that occur during prenatal and early postnatal development. As discussed in Chapter 3, Oour knowledge of the ways in which genes and the environment interact to affect the development of the brain has expanded by leaps and boundsrapidly. The years ahead will bring even more breathtaking progress as, for example, the completion of the human genome project provides a map of the genomereveals the details of all of our genes. This and this promises an explosion of our ability to understand the interweaving of genetic and environmental influences as they affect both brain and behavioral development.

The growth in “brain knowledge” naturally leads to demands to understand what this meansits implications for how we should raise children and what we can do to improve their development. Accordingly, efforts to translate this emerging knowledge for public consumption have proliferated in recent years. Some of these attempts have portrayed this information has been well and accurately portrayed; but some haves also been misportrayed it. The challenge of deciphering what this information means for what we should do as parents, guardians, and teachers of young children is enormous. There are few neuroscience studies of very young children and those that exist have not usually focused on the brain regions that affect cognition, emotions, and other complex developmental tasks that are of greatest interest to those who raise and care for them.

Much of our fundamental knowledge about brain development is actually based upon experimental studies in animals. The translation of this information from basic neuroscience into “rules” for application to humans can be quite straightforward when very similar mechanisms are involved in humans and animals, as is the case with the developing visual system. But, the interpretation of other data from animals, or even some data from humans (such as estimates of the density of synapses in various brain regions at various ages), can be extraordinarily complex or inappropriate when the brain mechanisms of cognition, language, and social-emotional development are addressed. In this context, it is essential to balance excitement about all that we are learning with caution about the limits of what we know understand today. This chapter’s synthesis of what science now tells us about the developing brain focuses on the role of experience in early brain development.. Four themes pertaining to experience run throughout this section:

1. While sSome important aspects of normal brain development require particular kinds of experience at particular points in development. However, for much of brain development, we either don’t know little much about these critical or sensitive periods, or it appears that the brain areas supporting particular competencies are open to experiences across broad stretches of development.

1. As far as we know, For normal development of our basic sensory systems, the kinds of experiences needed for our basic sensory systems to develop normally are appear to be so common that it is hard to find instances where they don’t existdo not occur. For most children, then, the question is less whether the environment is providing the necessary experience and more whether the child can detect or register the experience and process it adequately. Thus, for basic sensory systems, tThis shifts our the focus to early identification and treatment of problems such as visual impairments, auditory processing deficits, and major perceptual-motor delays., for exampleThese are examples of conditions, that truly do affect whether the child is getting can receive the usual stimulation needed to organize the developing nervous system.

1. We know far less about the environmental conditions that affect the development of brain systems that are critical for cognitive, language, and socio-emotional development. Seriously deleterious environments, such as those characterized by conditions of prolonged stress,severe malnutrition and maltreatment, are known to compromise the neurological mechanisms that underlie these more complex domains of development. Weknow very little have much to learn, however, about how the range of environments that lie between the obviously harmful and the obviously beneficial affect how the development of the young brain’s capacity functions to support how we learn, feel, and communicate with others.

BUT WE DO KNOW THAT THESE SYSTEMS DO REQUIRE EXPERIENCE AND, AT LEAST FOR SOME ASPECTS OF LANGUAGE DEVELOPMENT, THE TIMING OF THAT EXPERIENCE CAN BE PRETTY CRITICAL. SIMILARLY FOR SOCIAL – EMOTIONAL DEVELOPMENT, STRONG EVIDENCE SUGGESTS THE EXISTENCE OF REAL SENSITIVE PERIODS.

1. Although there has been great enthusiasm about studies of animals reared in “complex” or “enriched” environments, for reasons we will discuss, the animal research tells us less about what we can do to develop enhanced brains than it tells us about what we need to do to avoid disturbing or distorting the development of otherwise healthy brains. AS I SAID IN THE MEETING, DON’T THROW OUT A LOT OF DATA THAT SUGGESTS THAT THERE IS PROBABLY A FAIRLY LINEAR RELATIONSHIP BETWEEN INPUT AND IMPACT. THE ENVIRONMENTS AREN’T ENRICHED, BUT THE MESSAGE SHOULD NOT BE THAT “ABOVE SOME MINIMUM, EVERYTHING IS OK AND NOTHING EXTRA MATTERS.” A GREAT DEAL THAT WE KNOW ARGUES THAT THIS IS NOT TRUE AND THAT EXTRA DOES MATTER.

How Do We Study the Developing Brain?

Neuroscience techniques have advanced significantly, rendering studies of young children's brains more feasible and informative than in the recent past. These techniques have enabled scientists to learn more about how babies' brains change with development and how vulnerable or resilient they are to environmental insults. The repertoire of techniques that can be used with preschool-age and young children is circumscribed because some of the more direct methods (i.e., looking from inside the brain) of studying brains are either invasive (e.g., Positron Emission Tomopraphy requires the injection of a radioactive substance) or require long periods of still sitting (e.g., functional Magnetic Resonance Imaging). Nevertheless, by tracking the brain's activity from the outside with electroencephalograms, event-related potentials, and magnetic encaphalography, researchers can record the electrical activity of the brain while the baby or child is presented with different stimuli (e.g., speech sounds) and identify which parts of the brain are active and how active they are when children are "doing" different things. For example, this approach has been used to reveal that the neural substrate for recognizing faces and facial expressions is remarkably similar in the infant and the adult (ADD CITE), and that babies' brains change as they learn their native language (Kuhl, 19XX).

In addition, children with focal brain damage can be studied using neuropsychological tools that involve giving young children behavioral tasks that have been shown to depend on specific neural circuits (e.g., ADD EXAMPLE: simply memory tasks?) and observing how performance varies with the particular part of the brain that is damaged. This approach has been used in a longitudinal study of language development to demonstrate the remarkable resilience of children's language acquisition (ELABORATE AND ADD CITE). Finally, where parents have provided permission to use more invasive techniques, PET has revealed the patterns of synaptic growth and pruning that characterize early development (Chugani, 10XX) -- I ASSUME CHUGANI IS WORKING WITH NORMALLY DEVELOPING CHILDREN???? (see Appendix A for a fuller discussion of technologies for studying the developing human brain)

What “Develops” In Early Brain Development?

The development of the brain has a long trajectory, beginning within a few days after conception and continuing through adolescence. While the most dramatic development occurs during the first few years of life, the functional development of the brain that is made possible by the connections that are formed between and among its different areas takes years to complete. The milestones of brain development from the prenatal period up to school entry involve the development and migration of brain cells to where they belong functionally in the brain, embellishments of nerve cells through the sprouting of new axons or by expanding the dendritic surface; the formation of connections, or synapses, between nerve cells; and the postnatal addition of other cells types, notably glia. Fascination with the earliest stages of brain development is understandable. During this period, the spinal cord is formed, nearly all of the billions of neurons of the mature brain are produced, the dual processes of neural differentiation and cell migration establish their functional roles, and synaptogenesis proceeds apace.

There have been significant changes over time in the parameters of brain development that have captivated scientific and public attention. Twenty years ago, we were fascinated by our ability to measure developmental changes in when different areas of the brain became wrapped in the white, fatty matter—myelin—that insulates nerve cells and affects the speed with which nerve impulses are transmitted from one cell to another. Myelination is, in fact, affected by the young child’s behavioral experiences and nutrition, as we discuss below. Today, we are focused on information--not all of it new--about the rate of synapse development, particularly studies by Huttenlocher and his colleagues (detailed below) showing that there is a tremendous burst of synapse formation early in life followed by a decline in synapse number apparently extending into adolescence in some areas of the brain. Combined with evidence that those synapses that are used are retained and those not used are eliminated, there has been a frenzy of concern about “using it or losing it” in the first years of life. In comparison to the brain’s wiring, far less attention has been paid to the neurochemistry, or “juices”, of early brain development. Yet, the neurochemistry of brain development is essential to the brain’s capacity to learn from experience and is likely to play an important role in the regulation of behavior. We discuss this critical aspect of early brain development, as well.

Development of the Brain’s Wiring Diagram

Brain development proceeds in overlapping phases: makinge the brain cell (neurulation and neurogenesis), getting the cells to where they need to be in the brain (migration), growingtheir axons and dendrites—processes structures they need to link with other nerve cells (neurogenesisneuronal differentiation and pathfinding), developing synapses or points of communication with other cells (synaptogenesis), refineing those synapses (synaptic maturation and pruning), and, finally, forming the supportive tissue that surrounds the nerve cells and makes for efficient communication among them (glial-genesis or the production of myelin).

The brain and spinal cord arise from a set of cells on the back (dorsal part) of the developing embryo called the neural plate. Two rows of rapidly dividing cells arise from the plate on each side along its length and fold over centrally into the neural tube. The anterior or head end of the neural tube forms a set of swollen enlargements that give rise to the various parts of the brain—the forebrain containing the cerebral hemispheres, the midbrain containing important pathways to and from the forebrain, and the hindbrain containing the brainstem and cerebellum. The remainder of the neural tube becomes the spinal cord, peripheral nerves, and certain endocrine, or hormone, glands in the body. Under the control of regulatory genes, the brain cells migrate to where they belong in the brain in accord with the functions they will ultimately serve. These genes provide developmental directions to particular groups of cells, which tell them what to do and where to go in the embryonic brain. and the mature nervous system. The overall patterning of the developing nervous system is critically dependent on the expression of particular regulatory genes in particular regions of the brain as it developstBoth cell proliferation and migration vary from area to area but as a rule these processes are generally complete by six months (. CORRECT??). The exceptions to this rule include the cerebellum, whose development is more prolonged.

Within the neural tube, the innermost cells divide repeatedly, giving rise first to the cells that primarily become nerve cells, or neurons, and later giving rise to both neurons and the supportive tissue components called glia. Once the nerve cells are formed, they rapidly extend axons and dendrites and begin to form connections with each other, called synapses, often over relatively long distances. These connections allow nerve cells to communicate with each other. This process starts prenatally, but and continues well into the childhood years. In many, if not most, parts of the nervous system, the stability and strength of these synapses is determined to some degree by the activity, that is the firing, of these connections. The speed with which neurons communicate with each other across the synapses is determined by the development of myelin, a substance that wraps itself around nerve axons. By insulating the nerve cell axon, myelin increases conduction velocity. The development of myelin through the process of glialgenesis is a protracted developmental process extending well into the postnatal period. Most myelinated pathways are laid down in the first ten years, but myelination continues into the third decade of life. The unique “wiring diagram” that this process produces in each individual brain guides our thoughts, memories, feelings and behaviors.

Synaptic Overproduction and Loss

Beginning 20 years ago, the work of Rakic with monkeys (Rakic, Bourgeois, Eckenhoff, Zecevic, and Goldman-Rakic, 1986) and Huttenlocher with humans (e.g., Huttenlocher, 19798; Huttenlocher and Dabholkar, 1997) made landmark contributions to our understanding of the phenomenon of synapse development. Specifically, there is a pattern to synaptogenesis characterized by the rapid proliferation and overproduction of synapses, followed by a phase of synapse elimination or pruning that eventually brings the overall number of synapses down to their adult levels. This process is most exhuberant during the first few years of life, although it can extend well into adolescence. Within this developmental span, however, different brain regions with different functions appear to develop on different time courses (see Figure 1 – Nelson). Huttenlocher estimated that the peak of synaptic overproduction in the visual cortex occurs about midway through the first year of life, followed by a gradual retraction until the middle to the end of the preschool period, by which time the number of synapses has reached adult levels. In areas of the brain that subserve audition and language, a similar although somewhat later time course is observed. However, in the prefrontal cortex (the area of the brain where higher-level cognition takes place), a very different picture emerges. Here the peak of overproduction occurs at around one year of age, and it is not until middle to late adolescence that adult numbers of synapses are obtained[1].

Scientists have actually pondered the purpose of synaptic overproduction and loss for a very long time. One of the earliest observations was made by the turn of the century Nobel laureate Spanish neuroanatomist Santiago Ramon y Cajal:

“I noticed that every ramification, dendritic or axonic, in the course of formation, passes through a chaotic period, so to speak, a period of trials, during which there are sent out at random experimental conductors most of which are destined to disappear. …What mysterious forces precede the appearance of the processes, promote their growth and ramification … and finally establish those protoplasmic kisses, the intercellular articulations, which seem to constitute the final ecstasy of an epic love story?” [Recollections of My Life, 1917]