Thursday, July 01, 2004

How Truth Molds the Brain (and the Civilized Society)

The Physiology of Truth: Neuroscience and Human Knowledge

By: Pierre J. Magistretti, M.D., Ph.D.



The title chosen for this English translation of Jean-Pierre Changeux’s L’homme de Vérité is particularly apt. Changeux proposes a theory of the brain in which truth—experiences that confirm our ideas—literally operates on our genetic endowment to shape our brain development and functioning. How is this possible? Changeux hypothesizes the existence of neurobiological processes that are part of a kind of learning in which experience affects the brain’s cellular and molecular architecture. These neurobiological processes are constantly in operation in the brain, from the early stages of development into adult life. They make possible a permanent dialogue between the environment (our experience) and our brain, which frees the developing brain and mind from what would otherwise be the rigid constraints imposed by our genes.

The idea is timely. Amid the excitement about the unveiling of the human genome (as well as those of several other species), Changeux’s analysis strikes a sobering note. It pushes us to consider that the search for truth that characterizes scientific endeavors may be part of a permanent dialogue between us and our environment. Neuronal Man, the subject of an early seminal book of modern neuroscience by Changeux almost 20 years ago, thus returns and is at the center of this new and novel thesis. This new book, however, goes far beyond the neurobiological underpinnings of consciousness and human behavior. It poses the search for truth as a driving force and guiding principle for the establishment of individual freedom and even as a necessity for the consolidation of human rights. Science and the role of scientists are central in this quest; by establishing facts and their rational interpretation, scientists not only provide insights into the physical basis of nature but also help provide the knowledge that should ideally constitute the building blocks for a balanced development of societies. 

Taken out of context and briefly summarized, this statement may sound simplistic, reductionist, or simply grandiose. But to the reader who takes the time to follow Changeux’s well-constructed and pleasant-to-read argument, it becomes clear that it is the scientist’s obligation to expand his activity outside the walls of the laboratory to participate actively in the daily business of the res publica. Indeed, the book’s title could be The Physiology, Philosophy, and Sociology of Truth. The excellent quality of translation provided by Malcolm DeBevoise merits special notice. 


Let us first look at some hard science. In keeping with the rationalistic approach that characterizes Changeux’s scientific work, The Physiology of Truth first describes a set of experimental facts about brain function, then organizes them in an operative model. This working model is then subjected to additional experimental and computational testing, leading to further refinements. Thus, in the tradition of René Descartes, Immanuel Kant, and Louis Pasteur, the investigator poses theories and conceptual models that then give direction to further experimental enquiry. This contrasts with the view of empiricist philosophers such as Herbert Spencer, David Hume, and, more recently, Ernst Mach, for whom theory, if it is to be considered at all, should await the collection of data.

In a remarkable effort at popularization, taken in the noble sense of that word, Changeux reviews for the uninitiated the contrasting dogmas of rationalist and empiricist philosophy. This simplified philosophical explanation has its perfect place in the book, but it could also provide an inspiration to those who are in charge of defining academic curricula for undergraduate students in the natural sciences. They would benefit greatly from being at least aware of the fundamental philosophical approaches that have guided, and still guide, the scientific quest—or, to remain in the spirit of Changeux’s book, the search for true facts. 

The model of brain function, and, in particular, consciousness, proposed by Changeux is based on the existence of two broad types of neuronal systems. One, the processing neurons, is a network of parallel, distributed, and functionally specific systems that process primarily sensory and motor stimuli. This system is concerned with sensing external and internal signals and directing action. It is also concerned with long-term memory, self, and subjective personal experience, and it mediates motivation, reward, and emotions. 

A second neuronal system, at the core of the theory of the brain proposed by Changeux, is a set of neurons distributed throughout the cortex, and richly interconnected, that constitute a kind of workspace for processing information. At a given moment in our apprehension of reality, notably during tasks requiring a conscious effort and sustained attention, the widespread workspace neurons are jointly activated in various patterns. These patterns formed by neurons that are only transiently interconnected are the way we mentally represent objects or situations in the external world. What Changeux proposes here is not unlike the “neuronal assemblies” originally proposed in the 1940s by the Canadian psychologist Donald Hebb. 

Changeux’s theory is particularly original in suggesting how our mental representations of objects or situations might have a genetic dimension, what he calls “epigenetic.” Changeux’s hypothesis is that, before having any actual experiences, our brain can spontaneously generate pre-representations or prototype representations (caused genetically) that become the basis for the patterns of neuronal activity actually involved in experience. These pre-representations, also called by Changeux neural schemas or preliminary categories, are defined as spontaneous and transient states of activity of groups of neurons that at specific, restricted periods are able to act in synchrony. Changeux proposes that the number of pre-representations generated by the spontaneously active brain (that is, genetically) can be different from person to person. 

The theory is obviously not easy to summarize. Readers familiar with the philosophy of Kant, however, immediately see an alternative perspective on these pre-representations. They could be formed from the inherent, universal categories of all thought proposed by Kant. However, the pre-representations spontaneously generated by the brain, and reflecting what we could call internal reality, must be confronted by external reality in a test of truth. During the early development of infants, babbling, playing with objects, screaming, and calling are some of the activities (called by Changeux cognitive games) that could be manifestations of the pre-representations already genetically programmed in the brain. Whether or not one of these internally generated pre-representations becomes stabilized in the brain, however, depends on the nature of the signal received from the outside world. Usefulness, and the attendant rewards, consolidates a given pre-representation. Negative signals or punishment presumably have the opposite effect, extinguishing a pre-representation. On the basis of recent electrophysiologic and imaging data, Changeux suggests that workspace neurons are mostly located in the prefrontal cortex and are there actively engaged in reality testing of our pre-representations. 


An entire chapter about states of consciousness provides a compact yet complete treatment of current hypotheses about the neurobiology of consciousness, with here and there, as in other parts of the book, a stimulating philosophical angle. The chapter also supplies some of the premises for Changeux’s brain-workspace model. Unity of consciousness, our capacity to integrate various elements of the outside world detected by our senses, remains Changeux’s focus in this chapter. Notions such as the field of consciousness (proposed by the French psychiatrist Henry Ey) and the dynamic and continually changing stream of consciousness (discussed by William James) are stimulating attempts to capture the idea that consciousness is coherent and stable—providing an indispensable anchor for the identity of the self—and yet at the same time variable and dynamic. The model proposed by Changeux is a masterly attempt to define the neuronal architecture that gives consciousness this simultaneous coherence (the pre-representations) and variety (testing them against experience). 

The Physiology of Truth is filled with lucid descriptions of data from neurobiological, genetic, cell, and systems biology, supplying the information that allows Changeux to substantiate the models he proposes. As noted earlier, an incisive discussion of the usefulness of models in scientific endeavors provides a nice variation on the main theme of the book. In particular, neurobiologists should ponder Changeux’s review of the usefulness of models, including the long history of dialogue—and often controversy—between empiricism and rationalism, which have distinct and often opposed functions. Modern science could use both empiricism and rationalism to progress in the search for truth. 

What, then, of the search for truth in its role as a promoter of the freedom of people and of societies—a discussion that emerges toward the end of the book? Changeux makes a compelling case for scientists to participate in the public debate. Public awareness of science is indispensable to scientific progress. Changeux refers to the Agora of the Ancient Greeks: the marketplace that was an ideal location to exchange views, challenge ideas and facts, and dispel as much as possible myths and superstitions. Myths are by definition not substantiated by objective and rational treatment of sensory information that originates in the physical world. Nevertheless, myths provide explanations that are generally accepted by the group to which a person belongs. Sharing beliefs provides reference points that consolidate personal identity. 

Changeux proposes that this feeling of belonging, of shared confidence, can activate circuits in the brain, in particular those concerned with the expectation of rewards, known to use dopamine and the opiates as their neurotransmitters. This provocative point of view, which echoes Karl Marx’s characterization of religion as the opiate of the masses, stands in contradistinction to the central role of the test of reality in the epigenetic determination of brain function. Myths are permanently established dogmas, often remaining unchallenged; by contrast, scientific theory is dynamic and plastic, constantly being modified and adjusted to new evidence. Thus, the drive to identify objective facts independent of individual biases or accepted myths is not only a defining feature of the neurobiology of cognition but could also play a decisive role in establishing more just civil societies, which are more respectful of individual human rights. 

With this final, intriguing connection, The Physiology of Truth takes us on a journey beyond the rigorous description of biological phenomena and their modeling. Changeux opens new horizons by emphasizing the importance of science and scientists in the making of civilized societies. Once again he positions himself not only as one of the great scientists at the turn of the 20th century, but also as one of its great thinkers. 


From The Physiology of Truth: Neuroscience and Human Knowledge by Jean-Pierre Changeux. © 2004 by the President and Fellows of Harvard College. Reprinted with permission from Harvard University Press. 

The roughly 30,000 genes that make up the genetic endowment of the human species confer upon the brain the universal traits that make us human beings. The architecture of the brain in its main outlines is constrained, as we have seen, by an “envelope” of genes that govern its development. Even so, the human race is distinguished from other species by its remarkable ability to learn and conserve stable traces of past experience. In the course of evolution, this aptitude has grown to an extent unrivaled in the living world. Moreover, vestiges of man’s evolutionary past are still perceptible in the early stages of the brain’s development. 

In this chapter I wish to argue that the formation of the million billion synapses found in the adult brain escapes control by the genes to a limited extent, and that, to this extent, it is properly regarded as an epigenetic evolutionary process characterized by variation and selection that begins during embryonic development and continues after birth. The word “epigenetic” is composed of two Greek roots: epi, which means “on” or “upon,” and genesis, which means “birth.” Although the second term furnished the title of the first book of the Bible—the account of the creation of the world, of animals, and of man, as well as of the development of life on earth—the use of the word “genetics” to designate the science of heredity is recent. 

“Epigenetic,” in the sense in which I use the term, combines two meanings: the idea of superimposition upon the action of the genes, chiefly as a result of learning and experience; and the notion of coordinated and organized development. The neural systems of the brain are not in fact—I repeat the point because it is important—assembled after the fashion of a computer, with prefabricated parts fitted together in accordance with a blueprint that exactly specifies the nature and purpose of each circuit and switch. If this were the case, an error in even the smallest detail of the implementation of a program could have catastrophic consequences. As against an exclusively genetic conception of the brain as the embodiment of a strictly predetermined genetic inheritance, the epigenetic model postulates that the connections between neurons are established in stages, with a considerable margin of variability, and are subject to a process of selection that proceeds by means of trial and error.

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The opening of the genetic envelope to epigenetic variability and to evolution by selection is made possible, as we have seen, by the incorporation of a random component in synaptic development within cascading and nested sequences of synaptic outgrowth that begin in the earliest stages of embryogenesis and last until puberty. Each successive wave of connections, whose type and timing are very probably determined by the genetic envelope, is correlated with the acquisition of particular skills, but also with the loss of certain abilities (possibly due to top-down processes of selective inhibition). Innate knowledge and epigenetic learning are closely associated during pre- and postnatal development. This period is marked by a series of crucial events: the infant’s first applications of practical knowledge; the emergence of reflective consciousness and, subsequently, of a theory of mind; and the learning of language, epigenetic rules, and social conventions. Epigenesis makes possible the diversification, transmission, and evolution of culture. A sound education ought to supplement these developmental patterns with an appropriate basis for learning and experience. The individual character of each person is thus constructed as a function of what the sociologist Pierre Bourdieu called “habitus” —a unique synthesis of one’s genetic endowment, circumstances of birth and upbringing, and subjective experience of the social and cultural environment in which one has grown up. 

Both innate knowledge and innate disposition to acquire further knowledge— and to consciously test its truth—developed through the genetic evolution of species. The exceptionally long period of epigenetic evolution undergone by the human brain enabled it to incorporate information about the external world that is unobtainable by genetic mechanisms. This process also made possible the production of a cultural memory that is not directly subject to the intrinsic limitations of the brain, and so can be epigenetically transmitted at the level of the social group. In view of the considerable variability that epigenesis introduces in the neuronal network, however, the question arises how invariant and universal truths have been able to be discovered despite the multiplicity of personal experience and the diversity of human cultures—how, in a word, science is possible.

About Cerebrum

Bill Glovin, editor
Carolyn Asbury, Ph.D., consultant

Scientific Advisory Board
Joseph T. Coyle, M.D., Harvard Medical School
Kay Redfield Jamison, Ph.D., The Johns Hopkins University School of Medicine
Pierre J. Magistretti, M.D., Ph.D., University of Lausanne Medical School and Hospital
Helen Mayberg, M.D., Icahn School of Medicine at Mount Sinai 
Bruce S. McEwen, Ph.D., The Rockefeller University
Donald Price, M.D., The Johns Hopkins University School of Medicine
Charles Zorumski, M.D., Washington University School of Medicine

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