November 24, 2004
MIT team finds genetic key to high-level thinking
Where's the smart drugs...
A gene expressed only in brain areas responsible for high-level thinking and feeling may be key to the brain's ability to respond rapidly to new input, scientists at MIT's Picower Center for Learning and Memory and colleagues report in the Nov. 18 issue of Neuron. The finding may one day allow researchers to manipulate the level or speed at which people learn new information.
Elly Nedivi, the Fred and Carole Middleton Assistant Professor at MIT, Jeffrey Cottrell (MIT Ph.D. 2004), and colleagues from Yale University have identified for the first time a gene encoding a protein that may function as a modulating switch to fine-tune certain neurons' plasticity, or ability to change. In addition to shedding light on plasticity, understanding this protein may one day allow researchers to manipulate the level or speed at which people learn new information.
Neurons pass along information across a small gap called a synapse. The synapse consists of the neuron's presynaptic and postsynaptic endings and a space between them. The postsynaptic ending is dotted with neurotransmitter receptors that act like tiny receivers for chemical signals. Through a mechanism that is not well understood, these receptors appear and disappear. Maintaining these surface receptors is a critical aspect of neuronal function. More receptors allow increased cell activity, but too much activity can be toxic.
Nedivi's results suggest that candidate plasticity gene 2 (cpg2) and the protein it encodes--CPG2--are key in balancing receptor turnover.
The protein encoded by the candidate plasticity gene 2 exists only near synapses in the parts of the brain responsible for receiving and interpreting sensory information, analyzing information, reasoning, experiencing emotions and initiating movement. This gene "might be the link between levels of brain activity and the ability of the brain to respond to an increased level of activity," said Nedivi, who explores activity-regulating genes that are the driving force behind plasticity--or change--in the brain.
Endocytosis is a process through which a substance can get into a cell without passing through the cell membrane. The cell engulfs a protein and creates a little pouch, or vesicle, to hold it internally. The protein CPG2 regulates endocytosis, controlling the number of receptors at the postsynaptic site. The researchers observed the effects of knocking out the cpg2 gene. "Getting rid of CPG2 clearly perturbs the process," Nedivi said. In the absence of the protein, the number of vesicles increased, decreasing the number of receptors on the surface.
The more active the cell, the more CPG2 is used to clear the vesicles and internalize them at a faster rate, leaving fewer receptors on the surface. This could be a protective mechanism for the synapse, which would be overwhelmed with a too-high level of activity.
In addition to Nedivi and Cottrell, co-authors are Erzsebet Borok and Tamas L. Horvath of Yale University Medical School.
This work is supported by the National Eye Institute, the National Center for Research Resources and the National Institute of Diabetes and Digestive and Kidney Diseases.
Posted by Epiphany at 11:41 PM | Comments (85)
New Tools to Help Patients Reclaim Damaged Senses
VR and cybernetica
By SANDRA BLAKESLEE
Published: November 23, 2004
heryl Schiltz vividly recalls the morning she became a wobbler. Seven years ago, recovering from an infection after surgery with the aid of a common antibiotic, she climbed out of bed feeling pretty good.
"Then I literally fell to the floor," she said recently. "The whole world started wobbling. When I turned my head, the room tilted. My vision blurred. Even the air felt heavy."
The antibiotic, Ms. Schiltz learned, had damaged her vestibular system, the part of the brain that provides visual and gravitational stability. She was forced to quit her job and stay home, clinging to the walls to keep from toppling over.
But three years ago, Ms. Schiltz volunteered for an experimental treatment - a fat strip of tape, placed on her tongue, with an array of 144 microelectrodes about the size of a postage stamp. The strip was wired to a kind of carpenter's level, which was mounted on a hard hat that she placed on her head. The level determined her spatial coordinates and sent the information as tiny pulses to her tongue.
The apparatus, called a BrainPort, worked beautifully. By "buzzing" her tongue once a day for 20 minutes, keeping the pulses centered, she regained normal vestibular function and was able to balance.
Ms. Schiltz and other patients like her are the beneficiaries of an astonishing new technology that allows one set of sensory information to substitute for another in the brain.
Using novel electronic aids, vision can be represented on the skin, tongue or through the ears. If the sense of touch is gone from one part of the body, it can be routed to an area where touch sensations are intact. Pilots confused by foggy conditions, in which the horizon disappears, can right their aircraft by monitoring sensations on the tongue or trunk. Surgeons can feel on their tongues the tip of a probe inside a patient's body, enabling precise movements.
Sensory substitution is not new. Touch substitutes for vision when people read Braille. By tapping a cane, a blind person perceives a step, a curb or a puddle of water but is not aware of any sensation in the hand; feeling is experienced at the tip of the cane.
But the technology for swapping sensory information is largely the effort of Dr. Paul Bach-y-Rita, a neuroscientist in the University of Wisconsin Medical School's orthopedics and rehabilitation department. More than 30 years ago, Dr. Bach-y-Rita developed the first sensory substitution device, routing visual images, via a head-mounted camera, to electrodes taped to the skin on people's backs. The subjects, he found, could "see" large objects and flickering candles with their backs. The tongue, sensitive and easy to reach, turned out to be an even better place to deliver substitute senses, Dr. Bach-y-Rita said.
Until recently sensory substitution was confined to the laboratory. But electronic miniaturization and more powerful computer algorithms are making the technology less cumbersome. Next month, the first fully portable device will be tested in Dr. Bach-y-Rita's lab.
The BrainPort is nearing commercialization. Two years ago, the University of Wisconsin patented the concept and exclusively licensed it to Wicab Inc., a company formed by Dr. Bach-y-Rita to develop and market BrainPort devices. Robert Beckman, the company president, said units should be available a year from now.
Meanwhile, a handful of clinicians around the world who are using the BrainPort on an experimental basis are effusive about its promise.
"I have never seen any other device do what this one does," said Dr. F. Owen Black, an expert on vestibular disorders at the Legacy Clinical Research and Technology Center in Portland, Ore. "Our patients are begging us to continue using the device."
Dr. Maurice Ptito, a neuroscientist at University of Montreal School of Optometry, is conducting brain imaging experiments to explore how BrainPort works.
Dr. Eliana Sampaio, a neuroscientist at the National Conservatory of Arts and Métiers in Paris, is using the BrainPort to study brain plasticity. Sensory substitution is based on the idea that all sensory information entering the brain consists of patterns carried by nerve fibers.
In vision, images of the world pass through the retina and are converted into impulses that travel up the optic nerve into the brain. In hearing, sounds pass through the ear and are converted into patterns carried by the auditory nerve into the brain. In touch, nerve endings on skin translate touch sensations into patterns carried into the brain.
These patterns travel to special sensory regions where they are interpreted, with the help of memory, into seeing, hearing and touch. Patterns are also seamlessly combined so that one can see, hear and feel things simultaneously.
"We see with the brain, not with the eyes," Dr. Bach-y-Rita said. "You can lose your retina but you do not lose the ability to see as long as your brain is intact."
Most important, the brain does not seem to care if patterns come from the eye, ear or skin. Given the proper context, it will interpret and understand them. "For me, it happened automatically, within a few minutes," said Erik Weihenmayer, who has been blind since he was 13.
Mr. Weihenmayer, a 35-year-old adventurer who climbed to the summit of Mount Everest two years ago, recently tried another version of the BrainPort, a hard hat carrying a small video camera. Visual information from the camera was translated into pulses that reached his tongue.
He found doorways, caught balls rolling toward him and with his small daughter played a game of rock, paper and scissors for the first time in more than 20 years. Mr. Weihenmayer said that, with practice, the substituted sense gets better, "as if the brain were rewiring itself."
Ms. Schiltz, too, whose vestibular system was damaged by gentamicin, an inexpensive generic antibiotic used for Gram-negative infections, said that the first few times she used the BrainPort she felt tiny impulses on her tongue but still could not maintain her balance. But one day, after a full 20-minute session with the BrainPort, Ms. Schiltz opened her eyes and felt that something was different. She tilted her head back. The room did not move. "I went running out the door," she recalled. "I danced in the parking lot. I was completely normal. For a whole hour." Then, she said, the problem returned.
She tried more sessions. Soon her balance was restored for three hours, then half a day. Now working with the BrainPort team at the University of Wisconsin, Ms. Schiltz wears the tongue unit each morning. Her balance problems are gone as long as she keeps to the regimen.
How the device produces a lasting effect is being investigated. The vestibular system instructs the brain about changes in head movement with respect to the pull of gravity. Dr. Bach-y-Rita speculated that in some patients, a tiny amount of vestibular tissue might survive and be reactivated by the BrainPort.
Dr. Black said he had seen the same residual effect in his own pilot study. "It decays in hours to days," he said, "but is very encouraging."
Blind people who have used the device do not report lasting effects. But they are amazed by what they can see. Mr. Weihenmayer said the device at first felt like candy pop rocks on his tongue. But that sensation quickly gave way to perceptions of size, movement and recognition.
Mr. Weihenmayer said that on several occasions he was able to find his wife, who was standing still in an outdoor park, but he admitted that he also once confused her with a tree. Another time, he walked down a sidewalk and almost went off a bridge.
Nevertheless, he is enthusiastic about the future of the device. Mr. Weihenmayer likes to paraglide, and he sees the BrainPort as a way to deliver sonar information to his tongue about how far he is from the ground.
Dr. Ptito is scanning the brains of congenitally blind people who, wearing the BrainPort, have learned to make out the shapes, learned from Braille, of capital letters like T, B or E. The first few times they wore the device, he said, their visual areas remained dark and inactive - not surprising since they had been blind since birth. But after training, he said, their visual areas lighted up when they used the tongue device. The study has been accepted for publication in the journal Brain.
Dr. Ptito says he would like to see if he could teach his subjects how to read drifting letters like those in advertising displays. Not seeing motion is a big problem for the blind, he said.
In another approach, Dr. Peter Meijer, a Dutch scientist working independently, has developed a system for blind people to see with their ears. A small device converts signals from a video camera into sound patterns delivered by stereo headset to the ears. Changes in frequency connote up or down. Changes in pixel brightness are sensed as louder or softer sounds.
Dr. Yuri Danilov, a neuroscientist and engineer who works with Dr. Bach-y-Rita, said the research team had thought of dozens of applications for the BrainPort, which he called a "USB port to the brain."
In one experiment, a leprosy patient who had lost the ability to experience touch with his fingers was outfitted with a glove containing contact sensors. These were coupled to skin on his forehead. Soon he experienced the data coming from the glove on his forehead, as if the feelings originated in his fingertips. He said he cried when he could touch and feel his wife's face.
The federal government has also shown interest in sensory substitution technology. The Navy is exploring the use of a tongue device to help divers find their way in dark waters at night, said Dr. Anil Raj, director of the Institute for Human and Machine Cognition at the University of West Florida in Pensacola.
The sensors detect water surges, informing Navy Seals if they are following the correct course. The Army is thinking about sending infrared signals from night goggles directly to the tongue, Dr. Raj said.
In another application, student pilots have been fitted with body sensors attached to aircraft instruments. When the airplane starts to pitch or change altitude, they can feel the movements on their chests.
Sensory substitution technology may eventually help millions of people overcome their sensory disabilities. But the devices may also have more frivolous uses: in video games, for example.
Dr. Raj said the tongue unit had already been tried out in a game that involved shooting villains. "In two minutes you stop feeling the buzz on your tongue and get a visual representation of the bad guy," he said. "You feel like you have X-ray vision. Unfortunately it makes the game boring."
Posted by Epiphany at 10:22 PM | Comments (4)
Gene Tweak Ends Procrastination
Now in pill format. =)
Just in time for back-to-school season, researchers have turned procrastinating monkeys into workaholics by suppressing a gene that encodes a receptor for a key brain chemical.
The receptor, for the neurotransmitter dopamine, is important for reward learning. By suppressing it, researchers at the US National Institute of Mental Health (NIMH) in Bethesda, Maryland caused monkeys to lose their sense of balance between reward and the work required to get it.
"Like many of us, monkeys normally slack off initially in working toward a distant goal. They work more efficiently—make fewer errors—as they get closer to being rewarded," says Barry Richmond of the NIMH Laboratory of Neuropsychology. "But without the dopamine receptor, they consistently stayed on-task and made few errors, because they could no longer learn to use visual cues to predict how their work was going to get them a reward."
Receptor suppression
The ability to associate work with reward is thought to go awry in many mental disorders, says Richmond, including schizophrenia, mood disorders and obsessive-compulsive disorder (OCD).
"For example, people who are depressed often feel nothing is worth the work," says Richmond. "People with OCD work incessantly; even when they get rewarded they feel they must repeat the task. In mania, people will work feverishly for rewards that aren't worth the trouble to most of us."
For their study, Richmond and colleagues used a molecular technique to shut off expression of a gene encoding receptors called D2. They created a DNA antisense agent—a genetic mirror image that shuts off production of target proteins—and injected it into an area of the brain called the rhinal cortex. The area was targeted because it's rich in dopamine and was previously associated with reward learning. The antisense agent turned off D2 expression for several weeks.
Reward learning impaired
Injected monkeys had been trained to release a lever when a spot on a monitor turned from red to green. If they did it right, the spot turned blue. A gray bar on the monitor indicated their progress, and when they successfully completed a trial they would get a juice treat.
Before the gene tweak, the monkeys would make fewer errors as they got closer to receiving a reward. After the gene tweak, they couldn't associate visual cues with workload and therefore couldn't figure out how much more they had to work to get a reward.
"The monkeys became extreme workaholics, as evidenced by a sustained low rate of errors in performing the experimental task, irrespective of how distant the reward might be," says Richmond. "This was conspicuously out-of-character for these animals. Like people, they tend to procrastinate when they know they will have to do more work before getting a reward."
Besides helping researchers understand reward learning—and giving hope to procrastinators everywhere—the study also points to a new technique for exploring molecular aspects of behavior.
Posted by Epiphany at 07:26 AM | Comments (49)
The Cybernetic Manifesto
http://pespmc1.vub.ac.be/MANIFESTO.html
1.Philosophy
Philosophy is the putting of our thought and language in order. Philosophy is important. Philosophy is a part of our knowledge.
2.Knowledge
Cybernetic epistemology defines knowledge as the existence in a cybernetic system of a model of some part of reality as it is perceived by the system. A model is a recursive generator of predictions about the world which allow the cybernetic system to make decisions about its actions. The notions of meaning and truth must be defined from this perspective.
Knowledge is both objective and subjective because it results from the interaction of the subject (the cybernetic system) and the object (its environment). Knowledge about an object is always relative: it exists only as a part of a certain subject. We can study the relation between knowledge and reality (is the knowledge true or false, first of all); then the subject of knowledge becomes, in its turn, an object for another subject of knowledge. But knowledge in any form (a proposition, a prediction, a law), irrespective of any subject is a logical absurdity. A detailed development of cybernetic epistemology on the basis of these definitions is critical for the formalization of the natural science and natural philosophy, and the interpretation of mathematical systems.
3.Freedom, will, control
Cybernetic metaphysics asserts that freedom is a fundamental property of things. Natural laws act as constraints on that freedom; they do not necessarily determine a course of events. This notion of freedom implies the existence of an agency, or agencies, that resolve the indeterminacy implicit in freedom by choosing one of the possible actions. Such an agency is defined as a will. A will exercises control over a system when the freedom of that system is constrained by actions chosen by the will.
4.God
We understand God in the spirit of pantheism. God is the highest level of control in the Universe. God is for the Universe what human will is for human body. Natural laws are one of the manifestations of God's will. Another manifestation is the evolution of the Universe: the Evolution.
5.Metasystem transition
When a number of systems become integrated so that a new level of control emerges, we say that a metasystem has formed. We refer to this process as a metasystem transition.
A metasystem transition is, by definition, a creative act. It cannot be solely directed by the internal structure or logic of a system, but must always comes from outside causes, from "above".
6.Evolution
The metasystem transition is the quantum of evolution. Highly organized systems, including living creatures, are multilevel hierarchies of control resulting from metasystem transitions of various scales.
Major evolutionary events are large-scale metasystem transitions which take place in the framework of the trial-and-error processes of natural selection.
Examples include: the formation of self-duplicating macromolecules; formation of multicellular organisms; emergence of intelligent organisms; formation of human society.
7. Human intelligence
Human intelligence, as distinct from the intelligence of non-human animals, emerges from a metasystem transition, which is the organism's ability to control the formation of associations of mental representations. All of specifically human intelligence, including imagination, language, self-consciousness, goal-setting, humor, arts and sciences, can be understood from this perspective.
8.Social integration
The emergence of human intelligence precipitated a further, currently ongoing, metasystem transition, which is the integration of people into human societies. Human societies are qualitatively different from societies of animals because of the ability of the human being to create (not just use) language. Language serves two functions: communication between individuals and modeling of reality. These two functions are, on the level of social integration, analogous to those of the nervous system on the level of integration of cells into a multicellular organism.
Using the material of language, people make new --- symbolic - models of reality (scientific theories, in particular) such as never existed as neural models given us by nature. Language is, as it were, an extension of the human brain. Moreover, it is a unitary common extension of the brains of all members of society. It is a collective model of reality that all members of society labor to improve, and one that preserves the experience of preceding generations.
9.The era of Reason
We make a strong analogy between societies and neural, multicellular organisms. The body of a society is the bodies of all people plus the things made by them. Its "physiology" is the culture of society. The emergence of human society marks the appearance of a new mechanism of Universal Evolution: previously it was natural selection, now it becomes conscious human effort. The variation and selection necessary for the increase of complexity of the organization of matter now takes place in the human brain; it becomes inseparable from the willed act of the human being. This is a turning point in the history of the world: the era of Reason begins.
The human individual becomes a point of concentration of Cosmic Creativity. With the new mechanism of evolution, its rate increases manifold.
10.Global integration
Turning to the future we predict that social integration will continue in two dimensions, which we can call width and depth. On the one hand (width), the growth of existing cultures will lead to the formation of a world society and government, and the ecological unification of the biosphere under human control. The ethics of cybernetical world-view demands that each of us act so as to preserve the species and the ecosystem, and to maximize the potential for continued integration and evolution.
11.Human super-beings
On the other hand (depth), we foresee the physical integration of individual people into "human super-beings", which communicate through the direct connection of their nervous systems. This is a cybernetic way for an individual human person to achieve immortality.
12.Ultimate human values
The problem of immortality is the problem of ultimate human values, and vice versa.
Living creatures display a behavior resulting from having goals. Goals are organized hierarchically, so that in order to achieve a higher-level goal the system has to set and achieve a number of lower-level goals (subgoals). This hierarchy has a top: the supreme, ultimate goals of a creature's life. In an animal this top is inborn: the basic instincts of survival and reproduction. In a human being the top goals can go beyond animal instincts. The supreme goals, or values, of human life are, in the last analysis, set by an individual in an act of free choice. This produces the historic plurality of ethical and religious teachings. There is, however a common denominator to these teachings: the will to immortality. The animal is not aware of its imminent death; the human person is. The human will to immortality is a natural extension of the animal will for life.
13.Decline of metaphysical immortality
One concept of immortality we find in the traditional great religions. We designate it as metaphysical. It is known as immortality of soul, life after death, etc. The protest against death is used here as a stimulus to accept the teaching; after all, from the very beginning it promises immortality. Under the influence of the critical scientific method, the metaphysical notions of immortality, once very concrete and appealing, are becoming increasingly abstract and pale; old religious systems are slowly but surely losing their influence.
14.Creative immortality
Another concept of immortality can be called creative, or evolutionary. The idea is that mortal humans contribute, through their creative acts, to the ongoing universal and eternal process -- call it Evolution, or History, or God -- thus surviving their physical destruction. This uniquely human motive underlies, probably, all major creative feats of human history.
15.Cybernetic immortality
The successes of science make it possible to raise the banner of cybernetic immortality. The idea is that the human being is, in the last analysis, a certain form of organization of matter. This is a very sophisticated organization, which includes a high multilevel hierarchy of control. What we call our soul, or our consciousness, is associated with the highest level of this control hierarchy. This organization can survive a partial --- perhaps, even a complete --- change of the material from which it is built. It is a shame to die before realizing one hundredth of what you have conceived and being unable to pass on your experience and intuition. It is a shame to forget things even though we know how to store huge amount of information in computers and access them in split seconds.
16.Evolution and immortality
Cybernetic integration of humans must preserve the creative core of human individual, because it is the engine of evolution. And it must make it immortal, because for the purpose of evolution there is no sense in killing humans. In natural selection, the source of change is the mutation of the gene; nature creates by experimenting on genes and seeing what kind of a body they produce. Therefore, nature has to destroy older creations in order to make room for the newer ones. The mortality of multicellular organisms is an evolutionary necessity. At the present new stage of evolution, the evolution of human-made culture, the human brain is the source of creativity, not an object of experimentation. Its loss in death is unjustifiable; it is an evolutionary absurdity. The immortality of human beings is on the agenda of Cosmic Evolution.
17.Evolution of the human person
The future immortality of the human person does not imply its frozen constancy. We can understand the situation by analogy with the preceding level of organization.
Genes are controllers of biological evolution and they are immortal, as they should be. They do not stay unchanged, however, but undergo mutations, so that human chromosomes are a far cry from the chromosomes of primitive viruses.
Cybernetically immortal human persons may mutate and evolve in interaction with other members of the super-being, while possibly reproducing themselves in different materials. Those human persons who will evolve from us may be as different from us as we are different from viruses. But the defining principle of the human person will probably stay fixed, as did the defining principle of the gene.
18. How integration may occur
Should we expect that the whole of humanity will unite into a single super-human being?
This does not seem likely, if we judge from the history of evolution. Life grows like a pyramid; its top goes up while the basis is widening rather than narrowing. Even though we have seized control of the biosphere, our bodies make up only a small part of the whole biomass. The major part of it is still constituted by unicellular and primitive multicellular organisms, such as plankton. Realization of cybernetic immortality will certainly require some sacrifices --- a vehement drive to develop science, to begin with. It is far from obvious that all people and all communities will wish to integrate into immortal super-beings. The will to immortality, as every human feature, varies widely in human populations. Since the integration we speak about can only be free, only a part of mankind -- probably a small part - should be expected to integrate. The rest will continue to exist in the form of "human plankton".
19.Integration on the Cosmic scene
But it is the integrated part of humanity that will ultimately control the Universe. Unintegrated humanity will not be able to compete with the integrated part. This becomes especially clear when we realize that the whole Cosmos, not the planet Earth, will be the battlefield. No cosmic role for the human race is possible without integration. The units that take decisions must be rewarded for those decisions, otherwise they will never take them. Can we imagine "human plankton" crowded in rockets in order to reach a distant star in ten, twenty or fifty generations? Only integrated immortal creatures can conquer the outer space.
20.Current problems
At present our ideas about the cybernetic integration of humans are very abstract and vague. This is inevitable; long range notions and goals may be only abstract. But this does not mean that they are not relevant to our present concerns and problems. The concept of cybernetic immortality can give shape to the supreme goals and values we espouse, even though present-day people can think realistically only in terms of creative immortality (although -- who knows?).
The problem of ultimate values is the central problem of our present society. What should we live for after our basic needs are so easily satisfied by the modern production system? What should we see as Good and what as Evil? Where are the ultimate criteria for judging social organization?
Historically, great civilizations are inseparable from great religions which gave answers to these questions. The decline of traditional religions appealing to metaphysical immortality threatens to degrade modern society. Cybernetic immortality can take the place of metaphysical immortality to provide the ultimate goals and values for the emerging global civilization.
21.Integration and freedom
We are living at a time when we can see the basic contradiction of the constructive evolution of mankind very clearly: it is the contradiction between human integration and human freedom. Integration is an evolutionary necessity. If humanity sets itself goals which are incompatible with integration the result will be an evolutionary dead end: further creative development will become impossible. Then we shall not survive. In the evolving Universe there is no standstill: all that does not develop perishes. On the other hand, freedom is precious for the human being; it is the essence of life. The creative freedom of individuals is the fundamental engine of evolution in the era of Reason. If it is suppressed by integration, as in totalitarianism, we shall find ourselves again in an evolutionary dead end. This contradiction is real, but not insoluble. After all, the same contradiction has been successfully solved on other levels of organization in the process of evolution. When cells integrate into multicellular organisms, they continue to perform their biological functions--metabolism and fission. The new quality, the life of the organism, does not appear despite the biological functions of the individual cells but because of them and through them. The creative act of free will is the "biological function" of the human being. In the integrated super-being it must be preserved as an inviolable foundation, and the new qualities must appear through it and because of it. Thus the fundamental challenge that the humanity faces now is to achieve an organic synthesis of integration and freedom.
Posted by Epiphany at 07:18 AM | Comments (600)