Which parts of the brain actually use this auto-installation technique is another matter. The visual system does not appear to need the technique to grow topographically organized wiring; a rough topographic map develops under the direct control of the genes. Some neuroscientists believe that the fire-together-wire-together technique may still be used to make the maps more precise or to segregate the inputs from the two eyes.50 That, too, has been challenged, but let us assume it is correct and see what it means.
The fire-together-wire-together process could, in theory, be set in motion by letting the eyeballs gaze at the world. The world has lines and edges that stimulate neighboring parts of the retina at the same time, and that provides the information the brain needs to set up or fine-tune an orderly map. But in the case of Shatz’s cats, it works without any environmental input at all. The visual system develops in the pitch-dark womb, before the animal’s eyes are open and before its rods and cones are even hooked up and functioning. The retinal waves are generated endogenously by the tissues of the retina during the period in which the visual brain has to wire itself up. In other words, the eye generates a test pattern, and the brain uses it to complete its own assembly. Ordinarily, axons from the eye carry information about things in the world, but the developmental program co-opted those axons to carry information about which neurons come from the same eye or the same place in the eye. A rough analogy occurred to me when I watched the cable TV installer figure out which cable in the basement led to a particular room upstairs. He attached a tone generator called a “screamer” to the end in the bedroom and then ran downstairs to listen for the signal on each cable in the bouquet coming out of the wall. Though the cables were designed to carry a television signal upstairs, not a test tone downstairs, they lent themselves to this other use during the installation process because an information conduit is useful for both purposes. The moral is that a discovery that brain development depends on brain activity may say nothing about learning or experience, only that the brain takes advantage of its own information-transmission abilities while wiring itself up.
Fire-together-wire-together is a trick that solves a particular kind of wiring problem: connecting a surface of receptors to a maplike representation in the cortex. The problem is found not just in the visual system but in other spatial senses such as touch. That is because the problem of tiling a patch of primary visual cortex, which receives information from the 2-D surface of the retina, is similar to the problem of tiling a patch of primary somatosensory cortex, which receives information from the 2-D surface of the skin. Even the auditory system may use the trick, because the inputs representing different sound frequencies (roughly, pitches) originate in a 1-D membrane in the inner ear, and the brain treats pitch in audition the way it treats space in vision and touch.
But the trick may be useless elsewhere in the brain. The olfactory (smell) system, for example, wires itself by a completely different technique. Unlike sights, sounds, and touches, which are arranged by location when they arrive at the sensory cortex, smells arrive all mixed together, and they are analyzed in terms of the chemical compounds making them up, each detected by a different receptor in the nose. Each receptor connects to a neuron that carries its signal into the brain, and in this case the genome really does use a different gene for each axon when wiring them into their respective places in the brain, a thousand genes in all. It economizes on genes in a remarkable way. The protein produced by each gene is used twice: once in the nose, as a receptor to detect an airborne chemical, and a second time in the brain, as a probe at the end of the corresponding axon to direct it to its proper spot in the olfactory bulb.51
The wiring problems are different again for other parts of the brain, such as the medulla, which generates the swallowing reflex and other fixed action patterns; the amygdala, which handles fear and other emotions; and the ventromedial frontal cortex, which is involved in social reasoning. The fire-together-wire-together technique may be an ideal method for sensory maps and other structures that simply have to reproduce redundancies in the world or in other parts of the brain, such as primary sensory cortex for seeing, touching, and hearing. But other regions evolved with different functions, such as smelling or swallowing or avoiding danger or winning friends, and they have to be wired by more complicated techniques. This is simply a corollary of the general point with which I began the chapter: the environment cannot tell the various parts of an organism what their goals are.
The doctrine of extreme plasticity has used the plasticity discovered in primary sensory cortex as a metaphor for what happens elsewhere in the brain. The upshot of these two sections is that it is not a very good metaphor. If the plasticity of sensory cortex symbolized the plasticity of mental life as a whole, it should be easy to change what we don’t like about ourselves or other people. Take a case very different from vision, sexual orientation. Most gay men feel stirrings of attraction to other males around the time of the first hormonal changes that presage puberty. No one knows why some boys become gay—genes, prenatal hormones, other biological causes, and chance may all play a role—but my point is not so much about becoming gay as about becoming straight. In the less tolerant past, unhappy gay men sometimes approached psychiatrists (and sometimes were coerced into approaching them) for help in changing their sexual orientation. Even today, some religious groups pressure their gay members to “choose” heterosexuality. Many techniques have been foisted on them: psychoanalysis, guilt mongering, and conditioning techniques that use impeccable fire-together-wire-together logic (for example, having them look at Playboy centerfolds while sexually aroused). The techniques are all failures.52 With a few dubious exceptions (which are probably instances of conscious self-control rather than a change in desire), the sexual orientation of most gay men cannot be reversed by experience. Some parts of the mind just aren’t plastic, and no discoveries about how sensory cortex gets wired will change that fact.
WHAT IS THE brain actually doing when it undergoes the changes we call plasticity? One commentator called it “the brain equivalent of Christ turning water into wine” and thus a disproof of any theory that parts of the brain have been specialized for their jobs by evolution.53 Those who don’t believe in miracles are skeptical. Neural tissue is not a magical substance that can assume any form demanded of it but a mechanism that obeys the laws of cause and effect. When we take a closer look at the prominent examples of plasticity, we discover that the changes are not miracles after all. In every case, the altered cortex is not doing anything very different from what it ordinarily does.
Most demonstrations of plasticity involve remappings within primary sensory cortex. A brain area for an amputated or immobilized finger may be taken over by an adjacent finger, or a brain area for a stimulated finger expands its borders at the expense of a neighbor. The brain’s ability to reweight its inputs is indeed remarkable, but the kind of information processing done by the taken-over cortex has not fundamentally changed: the cortex is still processing information about the surface of the skin and the angles of the joints. And the representation of a digit or part of the visual field cannot grow indefinitely, no matter how much it is stimulated; the intrinsic wiring of the brain would prevent it.54
What about the takeover of the visual cortex by Braille in blind people? At first glance it looks like real transubstantiation. But maybe not. We are not witnessing just any talent taking over just any vacant lot in the cortex. Braille reading may use the anatomy of the visual cortex in the same way that seeing does.
Neuroanatomists have long known that there are as many fibers bringing information down into the visual cortex from other brain areas as there are bringing information up from the eyes.55 These top-down connections could have several uses. They may aim a spotlight of attention on portions of the visual field, or coordinate vision with the other senses, or group pixels into regions, or implement mental imagery, the ability to visualize things in the mind’s eye.56 Blind people may simply be using these prewired
top-down connections to read Braille. They may be “imagining” the rows of dots as they feel them, much as a blindfolded person can imagine objects placed in his hand, though of course far more rapidly. (Previous research has established that blind people have mental images—perhaps even visual images—containing spatial information.)57 The visual cortex is well suited to the kind of computation needed for Braille. In sighted people the eyes scan around a scene, bringing fine detail into the fovea, the high-resolution center of the retina. This is similar to moving the hands over a line of Braille, bringing fine detail under the high-resolution skin of the fingertips. So the visual system may be functioning in blind people much as it does in sighted ones, despite the lack of input from the eyes. Years of practice at imagining the tactile world and attending to the details of Braille have led the visual cortex to make maximal use of the innate inputs from other parts of the brain.
With deafness, too, one of the senses is taking over the controls of suitable circuitry, rather than just moving into any old unoccupied territory. Laura Petitto and her colleagues found that deaf people use the superior gyrus of the temporal lobe (a region near the primary auditory cortex) to recognize the elements of signs in sign languages, just as hearing people use it to process speech sounds in spoken languages. They also found that the deaf use the lateral prefrontal cortex to retrieve signs from memory, just as hearing people use it to retrieve words from memory.58 This should come as no surprise. As linguists have long known, sign languages are organized much like spoken languages. They use words, a grammar, and even phonological rules that combine meaningless gestures into meaningful signs, just as phonological rules in spoken languages combine meaningless sounds into meaningful words.59 Spoken languages, moreover, are partly modular: the representations for words and rules can be distinguished from the input-output systems that connect them to the ears and the mouth. The simplest interpretation, endorsed by Petitto and her colleagues, is that the cortical areas recruited in signers are specialized for language (words and rules), not for speech per se. What the areas are doing in deaf people is the same as what they are doing in hearing people.
Let me turn to the most amazing plasticity of all: the rewired ferrets whose eyes fed their auditory thalamus and cortex and made those areas work like a visual thalamus and cortex. Even here, water is not being turned into wine. Sur and his colleagues noted the redirected input did not change the actual wiring of the auditory brain, only the pattern of synaptic strengths. As a result they found many differences between the co-opted auditory brain and a normal visual brain.60 The representation of the visual field in the auditory brain was fuzzier and more disorganized, because the tissue is optimized for auditory, not visual, analysis. The map of the visual field, for instance, was far more precise in the left-right direction than in the up-down direction. That is because the left-right direction was mapped onto an axis of the auditory cortex that in normal animals represents different sound frequencies and thus gets inputs from the inner ear that are precisely arranged in order of frequency. But the up-down direction was mapped onto the perpendicular axis of the auditory cortex, which ordinarily gets a mass of inputs of the same frequency. Sur also notes that the connections between the primary auditory cortex and other brain areas for hearing (the equivalent of the wiring diagram for the visual system on page 88) were unchanged by the new input.
So patterns in the input can tune a patch of sensory cortex to mesh with that input, but only within the limits of the wiring already present. Sur suggests that the reason the auditory cortex in the rewired ferrets can process visual information at all is that certain kinds of signal processing may be useful to perform on raw sensory input, whether it is visual, auditory, or tactile:
On this view, one function of sensory thalamus or cortex is to perform certain stereotypical operations on input regardless of modality [vision, hearing, or touch]; the specific type of sensory input of course provides the substrate information that is transmitted and processed…. If the normal organization of central auditory structures is not altered, or at least not altered significantly, by visual input, then we might expect some operations similar to those we observe on visual inputs in operated ferrets to be carried out as well in the auditory pathway in normal ferrets. In other words, the animals with visual inputs induced into the auditory pathway provide a different window on some of the same operations that should occur normally in auditory thalamus and cortex.61
The suggestion that the auditory cortex is inherently suited to analyze visual input is not far-fetched. I mentioned that frequency (pitch) in hearing behaves a lot like space in vision. The mind treats soundmakers with different pitches as if they were objects at different locations, and it treats jumps in pitch like motions in space.62 This means that some of the analyses performed on sights may be the same as the analyses performed on sounds, and could be computed, at least in part, by similar kinds of circuitry. Inputs from an ear represent different frequencies; inputs from an eye represent spots at different locations. Neurons in the sensory cortex (both visual and auditory) receive information from a neighborhood of input fibers and extract simple patterns from them. Therefore neurons in the auditory cortex that ordinarily detect rising or falling glides, rich or pure tones, and sounds that come from specific places may, in the rewired ferrets, automatically be capable of detecting lines of specific slants, places, and directions of movement.
This is not to say that the primary auditory cortex can handle visual input right out of the box. The cortex still must tune its synaptic connections in response to the patterns in the input. The rewired ferrets are a remarkable demonstration of how the developing sensory cortex organizes itself into a well-functioning system. But as in the other examples of plasticity, they do not show that input from the senses can transform an amorphous brain into doing whatever would come in handy. The cortex has an intrinsic structure that allows it to perform certain kinds of computation. Many examples of “plasticity” may consist of making the input mesh with that structure.
ANYONE WHO HAS watched the Discovery Channel has seen footage of baby wildebeests or zebras falling out of the birth canal, wobbling on shaky legs for a minute or two, and then prancing around their mothers with their senses, drives, and motor control fully operational. It happens far too quickly for patterned experience to have organized their brains, so there must be genetic mechanisms capable of shaping the brain before birth. Neuroscientists were aware of this before plasticity came into vogue. The first studies of the development of the visual system by David Hubel and Torsten Wiesel showed that the microcircuitry of monkeys is pretty much complete at birth.63 Even their famous demonstrations that the visual systems of cats can be altered by experience during a critical period of development (by being reared in the dark, in striped cylinders, or with one eye sewn shut) show only that experience is necessary to maintain the visual system and to retune it as the animal grows. They do not show that experience is necessary to wire up the brain to start with.
We know in a general way how the brain assembles itself under the guidance of the genes.64 Even before the cortex has been formed, the neurons destined to make up different areas are organized into a “proto-map.” Each area in the proto-map is composed of neurons with different properties, molecular mechanisms that attract different input fibers, and different patterns of responses to the input. Axons are attracted and repelled by many kinds of molecules dissolved in the surrounding fluid or attached to the membranes of neighboring cells. And different sets of genes are expressed in different parts of the growing cortex. The neuroscientist Lawrence Katz has lamented that fire-together-wire-together has become a “dogma” keeping neuroscientists from exploring the full reach of these genetic mechanisms.65
But the tide is beginning to turn, and recent discoveries are showing how parts of the brain can organize themselves without any information from the senses. In experiments that the journal Science called “heretical,” Katz’s team removed one or both eyes from a
developing ferret, depriving the visual cortex of all its input. Nonetheless, the visual cortex developed with the standard arrangement of connections from the two eyes.66
Genetically engineered mice have provided especially important clues, because knocking out a single gene can be more precise than the conventional techniques of poisoning neurons or slicing up the brain. One team invented a mouse whose synapses were completely shut down, preventing neurons from signaling to one another. Its brain developed fairly normally, complete with layered structures, fiber pathways, and synapses in the right places.67 (The brain degenerated quickly after birth, showing again that neural activity may be more important in maintaining the brain than in wiring it.) Another team designed a mouse with a useless thalamus, depriving the entire cortex of its input. But the cortex differentiated into the normal layers and regions, each with a different set of turned-on genes.68 A third study did the opposite, inventing mice that were missing one of the genes that lay down gradients of molecules that help organize the brain by triggering other genes in particular places. The missing gene made a big difference: the boundaries among cortical areas were badly warped.69 The studies with knockout mice, then, suggest that genes may be more important than neural activity in organizing the cortex. Neural activity undoubtedly plays a role, which depends on the species, the stage of development, and the part of the brain, but it is just one capability of the brain rather than the source of its structure.