Work In Progress - How Much Do We Really Know About The Brain? | Inside The Teenage Brain | FRONTLIN

What are we learning about the brain's development as a result of new imaging technologies, such as functional magnetic resonance imaging?

Fischer: Functional MRI (fMRI) tells us about the location of major brain activity during a behavior, including not only in the cortex but also structures farther down in the brain. While fMRI gets the most publicity, several other new techniques make equally important contributions. The magnetoencephalogram (MEG) and the classical electroencephalogram (EEG) give the best information about brain activity over time as well as connections between cortical regions. The MEG tells us about brain activity in much the same way as the EEG, indicating the activity of neural networks in real time; but it gives more information than the EEG about deeper structures. Coherence analysis of EEG or MEG tells which parts of the brain are connected to each other by analyzing similarities in brain activity patterns. Combining information from these and other sources provides a much more complete portrait of brain functioning than has ever been possible.

Greenough: The principal news based upon both newer techniques like fMRI and other technologies is that the brain is a very dynamic place and continues to be so throughout development and even into adulthood. New synaptic connections continue to form between neurons throughout life. Patterns of myelination [the process by which brain cells are covered with a fatty white substance called myelin, which aids in the transmission of information between cells], while perhaps most dynamic from early development through adolescence, continue to change at least into the 4th decade of life. And blood vessels, the brain capillary networks in particular, respond to long-term changes in demand throughout much of adult life. Perhaps most exciting is that at least some regions of the brain continue to generate new neurons in adulthood, and those neurons appear to participate in the learning and memory process. Scientists first made these observations in animals and subsequently confirmed them in humans.

Thompson: These new imaging techniques provide extremely detailed pictures of the living brain, revealing how it grows and how its function changes though the teenage years, often in ways no one suspected.

Before brain imaging was invented, autopsy studies showed that older children had more of a fatty substance, called myelin, on their brain cells. This speeds up the electrical transmission of information between brain cells and is thought to make the brain more efficient as we go through the teen years. Earlier studies also revealed an exuberant growth of connections in the first two years of life, with a slow elimination of connections thereafter.

Now, imaging technologies let us visualize even more remarkable changes in the brains of children and teens. Using MRI scans, we can watch teenagers' brains change in miraculous patterns as they grow up. We recently created the first maps of brain growth in individual children and teens. To our surprise, an extraordinary wave of tissue growth spread through the brain, from front to back, between the ages of three and 15. Frontal brain circuits, which control attention, grew fastest from ages three to six. Language systems, which are further back in the brain, underwent a rapid growth spurt around the age of 11 to 15, and then drastically shut off in the early teen years. This language system growth is interesting, as it corresponds to the end of a period when we are thought to be most efficient at learning foreign languages. Perhaps the biggest surprise of all was how much tissue the brain loses in the teen years. Just before puberty, children lost up to 50 percent of their brain tissue in their deep motor nuclei -- these systems control motor skills such as writing, sports, or piano. This loss moves like a wildfire into the frontal lobes in late teens. We think it is a sign of rapid remodeling of brain tissue well into the teens and beyond.

In short, MRI scans provide the detail necessary to chart brain growth in individual children, and we are seeing new growth spurts, and surprising losses of cells much later than originally thought. It is as if a light has now lit up a huge landscape, and researchers are only just beginning to see the landmarks and features for the first time.

Siegel: Imaging techniques have provided a revolutionary new view into how the activation of neural circuits in the brain give rise to mental processes, such as memory, emotion, decision-making, and reasoning. The correlation of brain structure and function with the more subjective, but equally real, mental processes that define the mind enables us to deepen our understanding of how systems of neurons within the brain may give rise to how systems of neurons between brains function. This "interpersonal neurobiology" of understanding how the interaction of brain and human relationships shapes who we are is an exciting possibility in this new era of systems neuroscience.

How much do we know about the relationship between the anatomy or biology of the brain and behavior?

Fischer: We know much more because we are only now able to examine many dimensions of brain functioning in thriving human beings. Still, we do not know very much!

Key to our understanding is how the brain functions as a system -- for example, how neural networks grow and function across brain regions. Most of the recent advances in brain science have involved knowledge of the biology of single neurons and synapses, not knowledge of patterns of connection and other aspects of the brain as a system. In time the new imaging techniques will help scientists and educators to understand how brain and behavior work together, but we have a very long way to go.

Greenough: One thing that we know is that changes in the synaptic connections between neurons, whether involving newly-generated neurons in some brain regions or only pre-existing neurons in others, are a key part of the memory process.

Thompson: Interestingly, a surprising amount is already known. We know a lot about how the brain is organized anatomically and functionally. We know which parts are responsible for specific functions, such as spatial memory, emotion, vision, and language. We know a fair amount about how brain cells develop, how they speak to each other, what molecules are involved in learning and memory, and how they may be altered by disease or medication.

In looking at human brain development, several new techniques are now greatly accelerating our understanding of brain and behavior. Functional MRI, for example, is a new type of imaging technique that lets you see how, and where, the brain activates in response to learning new information, recognizing a face rather than just seeing a face, or learning new languages. These techniques allow you to find out exactly what changes in the brain when some types of information are learned, or when we perform different tasks such as speaking, or when we are ill.

Siegel: We are just beginning to identify how systems in the brain work together in an integrated fashion to create complex mental processes. The mind, which can be defined as a process that regulates the flow of energy and information, emanates from the activation of neuronal circuits. This flow, however, occurs not only within the skull, but also between two skulls (as in a "relationship"), and among many skulls (as in a family, or as in the Internet). For this reason, it is crucial in understanding the mind and its development that we embrace the exciting findings from brain science while exploring the reality that brain and mind are not the same. Since energy and information can flow beyond the boundaries of the skin-defined self, mind is a process that is beyond merely brain anatomy and biology. Behavior, and the mental processes that motivate it, are a product of the interface of the neurophysiological processes of the body and the interpersonal processes, of relationships, family, community, and the larger culture. These ideas are explored in my book The Developing Mind (Siegel, 1999). Recently, we have started an interdisciplinary research and education program at UCLA called the Center for Culture, Brain, and Development.

What are the most exciting or promising areas of research into brain development and learning and memory -- particularly pertaining to adolescents?

Siegel: The tremendously exciting findings of significant brain reorganization during the adolescent years has enabled us to begin to address some very important questions in a new light:

• Why do psychiatric illnesses so often emerge for the first time in adolescence?
• How and why do changes in brain function and structure correlate with adolescent cognitive and behavioral changes?
• Are there ways of examining our cultural approach to adolescence in a new light given the pruning and re-structuring of brain circuits during the teen years?

Regarding learning and memory, the relationships among factual and autobiographical memory suggest that we may be well served to have students integrate knowledge of the semantic (factual world) with self-knowledge (autonoesis) for more lasting and better remembered knowledge structures. The hippocampus has long been known as an important structure for explicit memory. Recent findings indicate that in some traumatized individuals, the hippocampus may become damaged -- possibly by way of excessive stress hormone, cortisol, secretion. This finding suggests that the legacy of trauma may then create cognitive impairments making school even more stressful for children who have experienced various forms of abuse or neglect. Awareness of these findings can help clinicians, educators, and policymakers to rethink how they approach individuals who have been victims of trauma.

The prefrontal cortex has an anatomic location that enables it to integrate a wide array of neural circuits into a functional whole. This process of integration enables the prefrontal area to play a central role in complex mental processes that emerge as the child grows. The dorsolateral prefrontal region is crucial for focal attention and working memory. The ventromedial prefrontal regions, also known as the orbitofrontal cortex because it sits behind the orbit of the eyes, is a crucial area involved in a wide array of processes such as social cognition (understanding the minds of others), attuned communication, self-regulation, response flexibility (taking in data, pausing, reflecting, and coming up with an adaptive, flexible response), and autobiographical memory and self-awareness.

The development of the prefrontal region may be responsive to patterns of social communication during the early years of life, and perhaps across the life span. Findings from recent studies of the changes in the adolescent brain point to the "off-line" status of this important integrative region. These findings may help us to gain insights into why teenagers act the way they so often do. As one of my patients said after doing an action with little thought -- "Don't forget, I am a teenager right now!" Action without reflection may often be a sign that the prefrontal cortex's response flexibility function is off-duty.

Fischer: Adolescents' brains show major developmental change, which new research is beginning to unravel. Behavioral scientists have documented in the last 25 years that adolescents undergo massive changes in cognitive and emotional capacities, and that these changes continue at least through early adulthood, well beyond the teen years. Brain scientists are now discovering similar changes in the brain. An essential question is how the major changes in brain connection and organization during adolescence and early adulthood relate to the established changes in cognitive capacities.

New cognitive capacities emerge at 10, 15, 20, and 25 years, in which young people become capable of using abstract concepts skillfully and relating them to each other in successively more complex ways. Younger children cannot use abstractions flexibly but instead reduce them to concrete instances and memorized definitions. At 9 to 10 years children become able to construct flexible abstract concepts, such as conformity, responsibility, and the operation of multiplication; but when they try to relate two abstractions to each other, they muddle them together. At about age 15 they can build flexible relations between a pair of abstractions and thus stop muddling them so badly. At age 19 or 20 they can build complex relations among multiple abstractions, and at 25 they can connect systems of abstractions to understand principles underlying them. Each of these developments involves the capacity to build a new kind of understanding, but that capacity is evident only in areas where young people work to construct their understanding -- the new abilities do not appear in all skills but only in those where the individual demonstrates optimal performance. A major challenge for neuroscientists is to understand how these emerging capacities relate to brain changes.

Thompson: My own view is that we now have an exciting array of techniques that are beginning to tell us, in exquisite detail, how the brain grows, and what changes to expect in healthy children and teens. We are also just beginning to compare these recently discovered brain changes with changes in autistic children, children with learning or communication disorders, and teenagers with emotional or psychiatric disorders.

The imaging techniques have tremendous promise for understanding how these enigmatic features of development emerge in healthy children and teens. Large-scale studies are now helping us exploit this technology and build a better picture of how the brain develops. Sometimes they reveal unsuspected features, such as the wave of brain tissue loss in the teen years. By studying this remodeling process, we hope to shed light on how this process might go awry in diseases that can strike in adolescence, such as schizophrenia.

But I think a second revolution in our understanding will come when we begin to bridge these brain imaging techniques with the powerful tools of the "Human Genome Project." In a recent study, we reported the first maps to visualize how genes affect brain structure -- in other words, which parts of the brain's hardware do we inherit from our parents, and which parts can change most in response to learning experiences and stimulation? A key focus is studying families of genes that are implicated in building our brains, and learning experiences that restructure them. As you read this, your brain is remodeling itself, but we know extremely little about what precisely is causing the changes. By developing new techniques to bridge imaging and genetics, a second revolution in our understanding will come. Only then we will go from observing brain changes in detail to understanding their causes. This in turn is likely to shed light on how developmental disorders might respond to new therapies, and what is happening in the healthy teenage brain.

What do you think are the difficulties and risks inherent in trying to translate neuroscience research into public policy for communities or advice for parents? What are the potential benefits?

Fischer: Ultimately neuroscience research will contribute enormously to our knowledge about raising and educating children, but right now we know too little to build public policy or advice on brain findings.

In contrast to neuroscience, cognitive science and developmental science are more mature, making enormous contributions to knowledge in the last 50 years. Much policy and advice can be based on that research, but neuroscience is too young to provide such specific guidance.

For example, in just the last few years basic "facts" about brain development have been overturned: Scientists believed that no new synapses or neurons could grow in adult brains, but recent research has challenged those beliefs, documenting the growth of both new neurons and new synapses in adults. Extensive research is required to understand how brains function and develop, to get beyond our current primitive state of knowledge.

When neuroscience connects to scientific knowledge about cognition and development, it can be helpful in a global way, supporting the cognitive developmental knowledge; but it cannot provide specific guidance on its own. With the excitement of the remarkable advances in biology and neuroscience in recent decades, people naturally want to use brain science to inform policy and practice, but our limited knowledge of the brain places extreme limits on that effort. There can be no "brain-based education" or "brain-based parenting" at this early point in the history of neuroscience!

Thompson: So long as research findings are interpreted carefully, there are enormous benefits to be gained. As we find out more about how the brain develops, our medical knowledge is enhanced, and the efficacy of new therapies can be evaluated in developmental disorders. A second goal is to help understand how we can optimally learn throughout life: in childhood, and in the teen years, are there are key times for learning specific skills? Is there a biological basis to support teaching children certain skills, such as mathematics, or foreign languages, at specific times? These are exciting questions. However, surprisingly little is known on these topics. Programs are emerging to help explore these questions scientifically. A potential danger is that findings from brain research can be overstretched, or used prematurely, to support particular learning aids, or commercial products. Parents should evaluate such claims with caution. Nonetheless, answers are likely to come from educators, parents and brain researchers working together on these questions, which may have substantial implications for social and educational policy.

Intriguingly, we know a lot more about factors that impair brain development, such as alcohol, drug abuse, and emotional deprivation, than about factors that promote healthy development or optimal learning. It is of paramount importance that we are aware, as a society, of the harmful effects on brain development that result from drug and alcohol abuse in the teenage years, and, in many countries worldwide, from malnutrition. These are key areas in which neuroscience research can provide backing, as well as supplementary information, to help guide policies that address these problems.

Siegel: I have been tremendously excited about the translation of findings not just in neuroscience, but in a wide range of academic disciplines studying development, such as anthropology, child psychology, linguistics, and systems theory, for the non-scientific audience. It has been deeply rewarding to first become immersed in these scientific fields, explore their similarities and differences, and then find the convergence of findings despite their differences in concepts, research methodologies, and vocabulary. The "consilience" (E.O. Wilson's term from the book of the same name, 1998) of findings enables an integrated view of the mind, brain, and human relationships to emerge. I have been amazed at how this interpersonal neurobiology of the developing mind has been useful to clinicians as well as parents, educators, clergy, and public policy makers. In recent publications, I have tried to offer some practical suggestions as to what the translation and integration of these scientific fields can offer.

There are many ways of exploring the implications for policy or education in noting the important connections among memory, emotion, relationships. Experience matters as the mind emerges from how the genetically programmed maturation of the nervous system responds to ongoing experience. Genes and experiences shape how neurons become connected to one another. One risk of over-interpreting the importance of experience can be found in the simplistic and potentially harmful suggestion for early and excessive amounts of sensory stimulation during infancy. Attachment research suggests that infants thrive not on excessive stimulation, but rather on forms of collaborative communication within interpersonal relationships that appear to promote emotional well-being. This collaborative, contingent form of communication can be taught to parents. The roots of possible difficulties parents experience with this form of communication can also be explored to enhance the nurturing and compassionate connections parents have with their own children. The integration of a systems view of neuroscience to understanding and promoting the development of children and adolescents has huge potential benefits for policy and practice.

Greenough: The results of neuroscience research cannot be translated into policy by itself. We have many sources of information regarding brain and behavioral development and learning. The best context for policy development is a team of individuals that collectively has expertise in child and adolescent development (especially developmental psychology), education, medicine (e.g., child psychiatry) and neuroscience. Working together to interpret the research and formulate policies that reflect the fullest possible knowledge of the development process, reasoned and valid policies can be proposed. A volume that comprises such an interdisciplinary report is "From Neurons to Neighborhoods: The Science of Early Childhood Development" published by the National Academy of Sciences. The potential benefits of policies that benefit or optimize human development are enormous, ranging from the economic effects of having a vastly more effective workforce to the societal and medical effects of a population that is as a whole better adapted to the demands of the 21st century lifestyle.