Moreover, the detailed arrangement of connections and synapses in a given region is a direct product of how extensively that region is used. As brain scanning has attained sufficiently high resolution to detect dendritic spine growth and the formation of new synapses, we can see our brain grow and adapt to literally follow our thoughts. This gives new shades of meaning to Descartes’ dictum “I think therefore I am.”
In one experiment conducted by Michael Merzenich and his colleagues at the University of California at San Francisco, monkeys’ food was placed in such a position that the animals had to dexterously manipulate one finger to obtain it. Brain scans before and after revealed dramatic growth in the interneuronal connections and synapses in the region of the brain responsible for controlling that finger.
Edward Taub at the University of Alabama studied the region of the cortex responsible for evaluating the tactile input from the fingers. Comparing nonmusicians to experienced players of stringed instruments, he found no difference in the brain regions devoted to the fingers of the right hand but a huge difference for the fingers of the left hand. If we drew a picture of the hands based on the amount of brain tissue devoted to analyzing touch, the musicians’ fingers on their left hand (which are used to control the strings) would be huge. Although the difference was greater for those musicians who began musical training with a stringed instrument as children, “even if you take up the violin at 40,” Taub commented, “you still get brain reorganization.”63
A similar finding comes from an evaluation of a software program, developed by Paula Tallal and Steve Miller at Rutgers University, called Fast ForWord, that assists dyslexic students. The program reads text to children, slowing down staccato phonemes such as “b” and “p,” based on the observation that many dyslexic students are unable to perceive these sounds when spoken quickly. Being read to with this modified form of speech has been shown to help such children learn to read. Using fMRI scanning John Gabrieli of Stanford University found that the left prefrontal region of the brain, an area associated with language processing, had indeed grown and showed greater activity in dyslexic students using the program. Says Tallal, “You create your brain from the input you get.”
It is not even necessary to express one’s thoughts in physical action to provoke the brain to rewire itself. Dr. Alvaro Pascual-Leone at Harvard University scanned the brains of volunteers before and after they practiced a simple piano exercise. The brain motor cortex of the volunteers changed as a direct result of their practice. He then had a second group just think about doing the piano exercise but without actually moving any muscles. This produced an equally pronounced change in the motor-cortex network.64
Recent fMRI studies of learning visual-spatial relationships found that interneuronal connections are able to change rapidly during the course of a single learning session. Researchers found changes in the connections between posterior parietal-cortex cells in what is called the “dorsal” pathway (which contains information about location and spatial properties of visual stimuli) and posterior inferior-temporal cortex cells in the “ventral” pathway (which contains recognized invariant features of varying levels of abstraction);65 significantly, that rate of change was directly proportional to the rate of learning.66
Researchers at the University of California at San Diego reported a key insight into the difference in the formation of short-term and long-term memories. Using a high-resolution scanning method, the scientists were able to see chemical changes within synapses in the hippocampus, the brain region associated with the formation of long-term memories.67 They discovered that when a cell was first stimulated, actin, a neurochemical, moved toward the neurons to which the synapse was connected. This also stimulated the actin in neighboring cells to move away from the activated cell. These changes lasted only a few minutes, however. If the stimulations were sufficiently repeated, then a more significant and permanent change took place.
“The short-term changes are just part of the normal way the nerve cells talk to each other,” lead author Michael A. Colicos said.
The long-term changes in the neurons occur only after the neurons are stimulated four times over the course of an hour. The synapse will actually split and new synapses will form, producing a permanent change that will presumably last for the rest of your life. The analogy to human memory is that when you see or hear something once, it might stick in your mind for a few minutes. If it’s not important, it fades away and you forget it 10 minutes later. But if you see or hear it again and this keeps happening over the next hour, you are going to remember it for a much longer time. And things that are repeated many times can be remembered for an entire lifetime. Once you take an axon and form two new connections, those connections are very stable and there’s no reason to believe that they’ll go away. That’s the kind of change one would envision lasting a whole lifetime.
“It’s like a piano lesson,” says coauthor and professor of biology Yukiko Goda. “If you play a musical score over and over again, it becomes ingrained in your memory.” Similarly, in an article in Science neuroscientists S. Lowel and W. Singer report having found evidence for rapid dynamic formation of new interneuronal connections in the visual cortex, which they described with Donald Hebb’s phrase “What fires together wires together.”68
Another insight into memory formation is reported in a study published in Cell. Researchers found that the CPEB protein actually changes its shape in synapses to record memories.69 The surprise was that CPEB performs this memory function while in a prion state.
“For a while we’ve known quite a bit about how memory works, but we’ve had no clear concept of what the key storage device is,” said coauthor and Whitehead Institute for Biomedical Research director Susan Lindquist. “This study suggests what the storage device might be—but it’s such a surprising suggestion to find that a prion like activity may be involved. . . . It . . . indicates that prions aren’t just oddballs of nature but might participate in fundamental processes.” As I reported in chapter 3, human engineers are also finding prions to be a powerful means of building electronic memories.
Brain-scanning studies are also revealing mechanisms to inhibit unneeded and undesirable memories, a finding that would gratify Sigmund Freud.70 Using fMRI, Stanford University scientists asked study subjects to attempt to forget information that they had earlier memorized. During this activity, regions in the frontal cortex that have been associated with memory repression showed a high level of activity, while the hippocampus, the region normally associated with remembering, was relatively inactive. These findings “confirm the existence of an active forgetting process and establish a neurobiological model for guiding inquiry into motivated forgetting,” wrote Stanford psychology professor John Gabrieli and his colleagues. Gabrieli also commented, “The big news is that we’ve shown how the human brain blocks an unwanted memory, that there is such a mechanism, and it has a biological basis. It gets you past the possibility that there’s nothing in the brain that would suppress a memory—that it was all a misunderstood fiction.”
In addition to generating new connections between neurons, the brain also makes new neurons from neural stem cells, which replicate to maintain a reservoir of themselves. In the course of reproducing, some of the neural stem cells become “neural precursor” cells, which in turn mature into two types of support cells called astrocytes and oligodendrocytes, as well as neurons. The cells further evolve into specific types of neurons. However, this differentiation cannot take place unless the neural stem cells move away from their original source in the brain’s ventricles. Only about half of the neural cells successfully make the journey, which is similar to the process during gestation and early childhood in which only a portion of the early brain’s developing neurons survive. Scientists hope to bypass this neural migration process by injecting neural stem cells directly into target regions, as well as to create drugs that promote this process of neurogenesis (creating new neurons) to repair brain damage from injury
or disease.71
An experiment by genetics researchers Fred Gage, G. Kempermann, and Henriette van Praag at the Salk Institute for Biological Studies showed that neurogenesis is actually stimulated by our experience. Moving mice from a sterile, uninteresting cage to a stimulating one approximately doubled the number of dividing cells in their hippocampus regions.72
Modeling Regions of the Brain
Most probably the human brain is, in the main, composed of large numbers of relatively small distributed systems, arranged by embryology into a complex society that is controlled in part (but only in part) by serial, symbolic systems that are added later. But the subsymbolic systems that do most of the work from underneath must, by their very character, block all the other parts of the brain from knowing much about how they work. And this, itself, could help explain how people do so many things yet have such incomplete ideas on how those things are actually done.
—MARVIN MINSKY AND SEYMOUR PAPERT73
Common sense is not a simple thing. Instead, it is an immense society of hard-earned practical ideas—of multitudes of life-learned rules and exceptions, dispositions and tendencies, balances and checks.
—MARVIN MINSKY
In addition to new insights into the plasticity of organization of each brain region, researchers are rapidly creating detailed models of particular regions of the brain. These neuromorphic models and simulations lag only slightly behind the availability of the information on which they are based. The rapid success of turning the detailed data from studies of neurons and the interconnection data from neural scanning into effective models and working simulations belies often-stated skepticism about our inherent capability of understanding our own brains.
Modeling human-brain functionality on a nonlinearity-by-nonlinearity and synapse-by-synapse basis is generally not necessary. Simulations of regions that store memories and skills in individual neurons and connections (for example, the cerebellum) do make use of detailed cellular models. Even for these regions, however, simulations require far less computation than is implied by all of the neural components. This is true of the cerebellum simulation described below.
Although there is a great deal of detailed complexity and nonlinearity in the subneural parts of each neuron, as well as a chaotic, semirandom wiring pattern underlying the trillions of connections in the brain, significant progress has been made over the past twenty years in the mathematics of modeling such adaptive nonlinear systems. Preserving the exact shape of every dendrite and the precise “squiggle” of every interneuronal connection is generally not necessary. We can understand the principles of operation of extensive regions of the brain by examining their dynamics at the appropriate level of analysis.
We have already had significant success in creating models and simulations of extensive brain regions. Applying tests to these simulations and comparing the data to that obtained from psychophysical experiments on actual human brains have produced impressive results. Given the relative crudeness of our scanning and sensing tools to date, the success in modeling, as illustrated by the following works in progress, demonstrates the ability to extract the right insights from the mass of data being gathered.
The following are only a few examples of successful models of brain regions, all works in progress.
A Neuromorphic Model: The Cerebellum
A question I examined in The Age of Spiritual Machines is: how does a ten-year-old manage to catch a fly ball?74 All that a child can see is the ball’s trajectory from his position in the outfield. To actually infer the path of the ball in three-dimensional space would require solving difficult simultaneous differential equations. Additional equations would need to be solved to predict the future course of the ball, and more equations to translate these results into what was required of the player’s own movements. How does a young outfielder accomplish all of this in a few seconds with no computer and no training in differential equations? Clearly, he is not solving equations consciously, but how does his brain solve the problem?
Since ASM was published, we have advanced considerably in understanding this basic process of skill formation. As I had hypothesized, the problem is not solved by building a mental model of three-dimensional motion. Rather, the problem is collapsed by directly translating the observed movements of the ball into the appropriate movement of the player and changes in the configuration of his arms and legs. Alexandre Pouget of the University of Rochester and Lawrence H. Snyder of Washington University have described mathematical “basis functions” that can represent this direct transformation of perceived movement in the visual field to required movements of the muscles.75 Furthermore, analysis of recently developed models of the functioning of the cerebellum demonstrate that our cerebellar neural circuits are indeed capable of learning and then applying the requisite basis functions to implement these sensorimotor transformations. When we engage in the trial-and-error process of learning to perform a sensorimotor task, such as catching a fly ball, we are training the synaptic potentials of the cerebellar synapses to learn the appropriate basis functions. The cerebellum performs two types of transformations with these basis functions: going from a desired result to an action (called “inverse internal models”) and going from a possible set of actions to an anticipated result (“forward internal models”). Tomaso Poggio has pointed out that the idea of basis functions may describe learning processes in the brain that go beyond motor control.76
The gray and white, baseball-sized, bean-shaped brain region called the cerebellum sits on the brain stem and comprises more than half of the brain’s neurons. It provides a wide range of critical functions, including sensorimotor coordination, balance, control of movement tasks, and the ability to anticipate the results of actions (our own as well as those of other objects and persons).77 Despite its diversity of functions and tasks, its synaptic and cell organization is extremely consistent, involving only several types of neurons. There appears to be a specific type of computation that it accomplishes.78
Despite the uniformity of the cerebellum’s information processing, the broad range of its functions can be understood in terms of the variety of inputs it receives from the cerebral cortex (via the brain-stem nuclei and then through the cerebellum’s mossy fiber cells) and from other regions (particularly the “inferior olive” region of the brain via the cerebellum’s climbing fiber cells). The cerebellum is responsible for our understanding of the timing and sequencing of sensory inputs as well as controlling our physical movements.
The cerebellum is also an example of how the brain’s considerable capacity greatly exceeds its compact genome. Most of the genome that is devoted to the brain describes the detailed structure of each type of neural cell (including its dendrites, spines, and synapses) and how these structures respond to stimulation and change. Relatively little genomic code is responsible for the actual “wiring.” In the cerebellum, the basic wiring method is repeated billions of times. It is clear that the genome does not provide specific information about each repetition of this cerebellar structure but rather specifies certain constraints as to how this structure is repeated (just as the genome does not specify the exact location of cells in other organs).
Some of the outputs of the cerebellum go to about two hundred thousand alpha motor neurons, which determine the final signals to the body’s approximately six hundred muscles. Inputs to the alpha motor neurons do not directly specify the movements of each of these muscles but are coded in a more compact, as yet poorly understood, fashion. The final signals to the muscles are determined at lower levels of the nervous system, specifically in the brain stem and spinal cord.79 Interestingly, this organization is taken to an extreme in the octopus, the central nervous system of which apparently sends very high-level commands to each of its arms (such as “grasp that object and bring it closer”), leaving it up to an independent peripheral nervous system in each arm to carry out the mission.80
A great deal has been learned in recent years about the role of the cerebel
lum’s three principal nerve types. Neurons called “climbing fibers” appear to provide signals to train the cerebellum. Most of the output of the cerebellum comes from the large Purkinje cells (named for Johannes Purkinje, who identified the cell in 1837), each of which receives about two hundred thousand inputs (synapses), compared to the average of about one thousand for a typical neuron. The inputs come largely from the granule cells, which are the smallest neurons, packed about six million per square millimeter. Studies of the role of the cerebellum during the learning of handwriting movements by children show that the Purkinje cells actually sample the sequence of movements, with each one sensitive to a specific sample.81 Obviously, the cerebellum requires continual perceptual guidance from the visual cortex. The researchers were able to link the structure of cerebellum cells to the observation that there is an inverse relationship between curvature and speed when doing handwriting—that is, you can write faster by drawing straight lines instead of detailed curves for each letter.
Detailed cell studies and animal studies have provided us with impressive mathematical descriptions of the physiology and organization of the synapses of the cerebellum,82 as well as of the coding of information in its inputs and outputs, and of the transformations performed.83 Gathering data from multiple studies, Javier F. Medina, Michael D. Mauk, and their colleagues at the University of Texas Medical School devised a detailed bottom-up simulation of the cerebellum. It features more than ten thousand simulated neurons and three hundred thousand synapses, and it includes all of the principal types of cerebellum cells.84 The connections of the cells and synapses are determined by a computer, which “wires” the simulated cerebellar region by following constraints and rules, similar to the stochastic (random within restrictions) method used to wire the actual human brain from its genetic code.85 It would not be difficult to expand the University of Texas cerebellar simulation to a larger number of synapses and cells.