2004 – XII

Neuroplasticity: The Neuronal Substrates of Learning and Transformation

October 18-22, 2004
Dharamsala, India

Train Your Mind, Change Your Brain An edited selection of dialogues from this conference has been published as Train Your Mind, Change Your Brain.

Overview

Neuroplasticity: Transforming the Mind by Changing the Brain

Neuroplasticity refers to structural and functional changes in the brain that are brought about by training and experience. The brain is the organ that is designed to change in response to experience. Neuroscience and psychological research over the past decade on this topic has burgeoned and is leading to new insights about the many ways in which the brain, behavior and experience change in response to experience. This basic issue is being studied at many different levels, in different species, and on different time scales. Yet all of the work invariably leads to the conclusion that the brain is not static but rather is dynamically changing and undergoes such changes throughout one’s entire life. The scientists assembled for this meeting represent the various levels of analysis in which these questions are being pursued. Research on structural plasticity will reveal how the literal composition of the adult mammalian brain is constantly changing and will show the factors that influence these changes.

Other studies at the molecular level reveal how the chemistry of DNA can be changed by experience in ways that affect the expression of our genes. Moreover, such effects on the chemistry of DNA can be produced by social experience, which in turn modifies gene expression in ways that can persist for the duration of a lifetime. These findings have radical implications for conceptualizing the dynamic interplay between nature and nurture. At more macro levels of brain systems, research will be discussed that demonstrates how sensory, perceptual and language functions are modified by experience and how the neural systems that underlie these complex behaviors are transformed through experiential alterations that occur early in life. Emotional function is also importantly shaped by experience and adult’s social relationships are shaped in part by early life experience. The ways in which these influences occur will be discussed and the brain mechanisms that might underlie such changes will be examined. Individuals differ in their characteristic ways of reacting to emotional situations.

Such individual differences may be importantly shaped by experience and by certain types of training. The role of contemplative training in transforming the emotional mind will be considered. A major question to be pursued over the course of this meeting will be the nature of mental training and its potential impact on the brain and behavior. Mental training appears to be emphasized much more in the contemplative traditions than it is in the Western scientific tradition. Another important issue for consideration is the optimal developmental periods to intervene to produce plastic changes to promote healthy functioning. Finally, the philosophical implications of this domain of science will be considered. Specifically, how should we conceptualize the impact of voluntary mental activity as influencing brain function?

Download the MLXII: Neuroplasticity Brochure PDF

Scientific Coordinator

Richard J. Davidson, Ph.D., Vilas Research Professor and William James Professor of Psychology and Psychiatry, University of Wisconsin-Madison

Participants

Tenzin Gyatso, His Holiness, the XIVth Dalai Lama of Tibet
Richard J. Davidson, Ph.D., Vilas Research Professor and William James Professor of Psychology and Psychiatry, University of Wisconsin-Madison
R. Adam Engle, J.D., M.B.A., CEO and Chairman of the Mind & Life Institute, and General Coordinator of the Mind & Life conferences
Fred H. Gage, Ph.D., Adler Professor, Laboratory of Genetics, The Salk Institute, San Diego
Michael J. Meaney, Ph.D., James McGill Professor, McGill University, Montreal
Kazuo Murakami, Ph.D., Emeritus Professor, Tsukuba University, Tsukuba, Japany
Helen J. Neville, Ph.D., The Robert and Beverly Lewis Endowed Chair, University of Oregon
Matthieu Ricard, Ph.D., Author and Buddhist monk at Shechen Monastery in Kathmandu and French interpreter since 1989 for His Holiness the Dalai Lama
Phillip R. Shaver, Ph.D., Professor and Chair of the Department of Psychology, University of California, Davis
Evan Thompson, Ph.D., Canada Research Chair in Cognitive Science and the Embodied Mind, York University, Toronto

Interpreters

Geshe Thupten Jinpa, Ph.D., President and Chief Editor for The Classics of Tibet Series produced by the Institute of Tibetan Classics in Montreal
B. Alan Wallace, Ph.D., President, The Santa Barbara Institute for Consciousness Studies

DAY 1:

Richard J. Davidson, the scientific coordinator of ML XII, will briefly introduce the week’s framework and objectives. He will give a brief overview of the perspectives to be brought to bear on neuroplasticity, and act as meeting moderator.

Presentation: Structural Changes in the Adult Brain in Response to Experience
Fred H. Gage

For those of us who study the nervous system, the brain is the organ of the body that controls our behavior. This belief means that what we think and what we do, while obviously influenced by the experiences we have, are the result of the brain’s processing of information and directing action. Given this basic assumption, the most common model or analogy of how the brain works is that of a computer. While this analogy may have some heuristic value, it is likely wrong or at least very limiting. The brain is an organ, like the liver, heart and kidney; it is made of chemicals, cells and tissue. The brain functions through individual cells communicating electrically and chemically. The real challenge for the neurons in the brain is calculating (interpreting) this temporally and spatially transmitted information and sending that interpreted message on to the next neurons in a circuit. The aggregation of this information passing and processing results in thinking and behaving.

One of the main arguments for developing the analogy of the brain as a stable machine or computer was that it helped to explain how we can remember things from one instance to the next. How could we do that if the underlying structure of the brain were changing all the time? For that matter, if the brain is the seat of consciousness (F. Crick), how can we maintain a self identity if the brain is not stable. However, we have learned that the brain is not physically stable, and that is probably a good thing. The structural instability that we have documented in the brain may be required to provide the extra capacity that is necessary for dealing with complexity and to provide the underpinning for the adaptability and flexibility, or “plasticity” (as neuroscientists refer to it), that is required for dealing with the variety of ever-changing challenges that we are faced with throughout our entire life.

I will summarize our current understanding of the structural plasticity that persists in the adult mammalian brain and discuss the experiences, behavior patterns, and drugs that can change our brain and, therefore, our behavior.

DAY 2:

Presentation: Experience-Induced Alterations in Gene Expression: The Impact of Early Experience on Emotional Functioning
Michael J. Meaney

The “nature-nurture” debate, which so preoccupies Western science, is essentially an argument of the relative importance of genetic versus environmental (or perhaps experiential) in the definition of individual differences among members of the same species. It is also an argument that is based on a fundamental misunderstanding of cell biology, for adherents commonly ignore the simple fact that neither genes nor experience can influence development independent of context. Experience requires translation through processes associated with bodily function that commonly includes brain activation. Such functions are inevitably influenced by the genome. Likewise, genes operate within cells, the activity of which is constantly regulated by external events. Alas, gene and experience are inseparable.

The nucleotide sequences that comprise the genome exist within a dynamic context that is constantly subject to modification. DNA is commonly found wrapped around histone proteins, and individual nucleotides are modified by the addition of various chemical groups. Hence, we speak of the chemistry of the DNA. Such chemical modifications of the DNA can permanently alter the activity of individual genes. The chemistry of the DNA in some cells will differ from that of others, which is why, despite containing exactly the same genes, liver cells function very differently from brain cells. Variations in the chemistry of the DNA can explain not only why cells within the same body operate differently, but also why the same cells in two different bodies vary in their function – the issue of individual differences.

Differences between individuals in the chemistry of the DNA are influenced by environmental events occurring early in development. An example of such effects is found in the study of DNA methylation, in which a methyl group is added onto individual cytosines within selected DNA sequences. This chemical modification is commonly associated with the stable silencing the gene within that cell. In the rat, maternal care of pups over the first week of life directs the process of DNA methylation in specific cells in the brain, thus permanently altering the activity of neurons, and thus cognitive and emotional functions.

These findings provide but one example of the interaction between gene and environment. We know little about whether such effects are resistant to reversal through experience at later stages of the lifespan; however, the basic elements of the process whereby maternal care alters the DNA and its activity suggest that such effects could occur at any stage of life, under the appropriate levels of stimulation. Such a continuous process of DNA modification could provide the functional interface between a static genome and a dynamic environment, allowing for adaptation within functional gene networks in a manner comparable to way synaptic plasticity forms the basis for adaptation within neuronal networks.

DAY 3:

Presentation: Human Developmental Plasticity
Helen J. Neville

“Experience shapes human brain development and function”
In this talk I will describe:

  1. the structure and function of the human brain and methods scientists use to study the human brain
  2. the long time course over which the human brain develops
  3. several studies that show how experience (i.e. input from the environment) affects the brain systems important for sensory processing, language processing, learning, intelligence, social and emotional skills
  4. the implications these discoveries have for health, education and support programs for children.

Scientists who study the brain have made many discoveries recently about how the brain works and how it develops. At birth the brain is very immature. In fact, the human brain is not fully mature until at least twenty years after birth. Moreover, during this long development the human brain is highly dependent on and is modified and shaped by experience. For example in people born blind the parts of the brain that normally process visual information are rewired and come to process sounds, including language. In those born deaf the areas of the brain that normally process sounds come to process vision.

The language relevant brain systems are also shaped by experience. In people who learn a language later than 6 years of age, the brain systems that normally process grammar are not recruited. However the brain systems that process the meanings of words are normal in late language learners. Children whose caregivers talk to them regularly display good language skills and well organized language brain systems. However children who are rarely spoken to have stunted language development and immature language brain systems.

Typical human and animal environments are complex and research has shown that such stimulating environments lead to enhanced brain growth, learning and intelligence. Furthermore, studies of animals and humans have shown that nurturing caregivers and low levels of stress are important in producing appropriate levels of the brain chemicals that are necessary for healthy emotional control. High levels of stress and the absence of nurturant caregivers result in high levels of the chemicals that are harmful to these systems.

In summary, contrary to what many people used to think, the human brain is a constantly changing, highly dynamic organ. Brain research can help guide people who care about children to design programs and services that optimize human development. Discussion will focus on the issue of sensitive developmental periods for the induction of specific forms of plasticity, the role of sensory, attentional, cognitive and social/emotional experience in producing plastic changes in the structure and function of the cortex. We seek input from the Buddhist scholars on the time periods during human development when different types of attentional/mindfulness training might help to optimize the development of the human potential in order to make the world a better place.

DAY 4:

Morning Presentation: Altering Attachment Security to Enhance Compassion and Altruism
Phillip R. Shaver (with Mario Mikulincer)

Over the past 30 years, developmental, personality, and social psychologists have been extending and testing attachment theory, a psychological theory first proposed in the 1960s and 70s by John Bowlby, a British psychiatrist, and Mary Ainsworth, an American developmental psychologist. The theory, rooted in both psychoanalytic psychiatry and primate ethology, deals with what Bowlby and Ainsworth called “attachment” (or emotional bonding) between infants and their primary caregivers (usually, but not necessarily, the biological mother). Depending on parental sensitivity and responsiveness (or insensitivity and unresponsiveness) to an infant’s distress signals, children can become relatively securely or insecurely attached to their primary caregivers, and if insecurely attached, can exhibit anxious, avoidant, or disorganized attachment behavior. The pattern of insecurity displayed during infancy has been shown to persist in many cases over periods of years, with continuing effects on mental health and success or failure in close personal relationships. Despite the tendency toward persistence, developmental and clinical researchers have successfully designed early intervention techniques to increase children’s sense of security.

In my work with Mario Mikulincer and our students, attachment theory is being applied to the study of adolescents’ and adults’ mental health and close relationships, such as friendship, romantic love, and marriage. We have found it possible to activate what Bowlby and Ainsworth called “the attachment behavioral system” experimentally, increasing a person’s sense of security by both conscious and unconscious means. By showing that a person’s “attachment style” (i.e., his or her characteristic pattern of security or insecurity) can be modified experimentally, we have been able to suggest ways to alter personality in the direction of increased security, even during adulthood.

Besides postulating the existence of an attachment behavioral system, an idea that has now been extensively researched, Bowlby also discussed other core behavioral systems, including exploration, caregiving, and sex. The caregiving system, which is most evident in parental sensitivity and responsiveness to young children, is the one that responds generally to other people’s needs and distress. Theoretically, therefore, it is the locus and source of compassion. Bowlby claimed that attachment-system activation (in response to threats or stressors) interferes with the optimal operation of the other behavioral systems, so that creating a boost in attachment security might foster, or allow, greater compassion (i.e., caregiving). New evidence related to this will be presented and similarities and differences between attachment theory and Buddhist psychology in conceptions of attachment, compassion, and personal plasticity (i.e., constructive personality change) will be explored.

Afternoon Presentation: Laughter Regulates Blood Glucose Levels and Gene Expression
Kazuo Murakami

It is well known that genes have the function of transmitting information necessary for the existence of living things from one generation to the next. An important role of the gene is to transcribe DNA information into RNA(mRNA),which is translated into protein. The rate-limiting step in the entire process from DNA to protein is from DNA to mRNA; thus, increase or decrease in the expression level of mRNA is called ON or OFF of the gene, and this ON/OFF of the gene is regulated by many factors.Many factors, such as physical factors (heat, pressure, tension, training, and exercise) and chemical factors including nutrients in food, alcohol, smoking, and endocrine disrupters are well known. Based on the fact that genes are switched ON/OFF by physical or chemical factors, I have proposed the hypothesis that mental factors are also involved in switching genes ON/OFF. I consider that these mental factors include not only negative mental stress, but also positive factors such as positive emotion, excitement, joy, gratitude, affection, belief, and spiritual feeling. To confirm my hypothesis, we study the effect of laughter an indicator of positive emotion, in terms of gene expression (ON/OFF) changes. We found that laughter lowered the increase in post prandial (after meal) blood glucose (PPBG) in the patient of type II diabetes in which only 23 genes out of 18,716 genes were up-regulated by more than 2-fold, however, no gene was down regulated by less than 0.5 fold in the peripheral blood leukocytes.

Contrary to expectations, these up-regulated genes did not include genes directly involved in blood glucose regulation, but included a candidate for suggesting the mechanism for suppressing the increase in blood glucose level. Dopamine D4 receptor gene (DRD4), which is linked to inhibition of adenylyl cyciase, was characterized by up-regulation on an average of 2.5-fold in the group with suppressed increases in PPBG. We speculate that the up-regulation of DRD4 by laughter leads to not only the deterioration of the increase in blood glucose via adenylyl cyclase, but also the improvement of poor glycemic control due to negative emotions.

DAY 5:

Presentation: Transforming the Emotional Mind: Perspectives from Affective Neuroscience
Richard J. Davidson

Our emotional reactions to events and our daily mood form the basis of our personality and color virtually all our behavior. Adult personality is traditionally regarded as relatively fixed and immutable. Research over the past decade on the brain mechanisms that subserve emotion and individual differences in emotional reactivity that we call affective style, have provided a new avenue to explore the possibility of emotional transformation in light of brain plasticity.This presentation will begin with a discussion of what we mean by affective style and how it can be measured. Rather than being conceptualized as a fixed trait, affective style is regarded as a trainable skill. Evidence that exposure to adversity can actually help to cultivate resilience will be presented. One of the specific characteristics that can be learned is emotion regulation. Even very short-term training in emotion regulation can produce demonstrable effects on brain function. Other forms of affective plasticity will also be described.

The presentation will end with a consideration of whether purely mental training can be used to transform emotion. New evidence from studies with highly skilled meditators will be presented to show that they can voluntarily alter brain function through mental practices. Questions that will be considered in discussion include the role of mental training versus behavioral training in transforming the emotional mind; whether particular developmental periods are optimal for training emotional skills; the matching of specific training regimes to individual differences in affective style; and whether training that results in increased contentment dampens motivation for social change.

Philosophical Presentation: Neuroplasticity and Neurophenomenology
Evan Thompson

For many years, Western mind science investigated cognitive processes, such as reasoning, perception, imagery, and attention, with little or no concern for subjective experience. In recent years, however, this attitude has begun to change, so that today there is increasing scientific interest, especially in affective-cognitive neuroscience, in understanding the experiential aspects of mental processes. For real progress to be made in this area, however, scientists must rely on detailed first-person reports about subjective experience. Yet exactly how such reports should be integrated into the conceptual framework and experimental procedures of mind science is still not clear.Research on plasticity offers an important context for considering this issue. On the one hand, it stands to reason that people vary in their abilities as observers and reporters of their own mental lives, and that these abilities can be enhanced through mental training of attention, emotion, and metacognition. Contemplative practice is a vehicle for precisely this sort of cognitive and emotional training. On the other hand, it stands to reason that mental training should be reflected in changes to brain structure, function, and dynamics. Hence contemplative practice could become a research tool both for developing better phenomenologies of subjective experience and for investigating the brain and neuroplasticity. This incorporation of contemplative practice into neuroscientific research would constitute a kind of experiential neuroscience or “neurophenomenology.”

This neurophenomenological approach raises several important questions for Western mind science and the science/Buddhism dialogue. First, it is well known in Western psychology that first-person reports, especially introspective or metacognitive ones, are subject to certain sorts of systematic biases. Is there reason to think that contemplative training can modify these biases? Second, if observing one’s mental life changes the character of one’s experience, then is there not a kind of “measurement problem” in using mental training to investigate experience? For instance, if metacognitive monitoring of first-order experience changes that experience, then how can one use metacognition to draw conclusions about experience independent of the monitoring act?

Finally, what is the best theory or model to explain how sustained voluntary activity on the part of the person (the whole embodied being aware of the world) can be causally efficacious at the level of neurons and neural assemblies? This last question is an aspect of the well-known, outstanding “explanatory gap” in the neuroscience of consciousness: On the one hand, the assumption that mental processes are brain processes both regulates (or guides) scientific research and constitutes the overall scientific view of the mind. One the other hand, there is still no adequate explanation of how brain activity gives rise to consciousness and of what causal role consciousness may play in the brain’s workings.