Connectome (20 page)

In the 1960s and 1970s David Hubel and Torsten Wiesel investigated these questions with experiments on kittens. To simulate amblyopia, they occluded vision in one eye, a condition they called “monocular deprivation.” Several months later they removed the occlusion and tested visual capability. The kittens could not see well with the previously deprived eye, much like human patients with amblyopia. To find out what had changed in the brain, Hubel and Wiesel recorded spikes from neurons in Brodmann area 17. Since this cortical area is important for vision, it's also known as primary visual cortex or V1. They measured the responsiveness of each neuron to visual stimulation of the left eye alone, and of the right eye alone. Few neurons responded to stimulation of the previously deprived eye.

The functions of V1 neurons had been altered by monocular deprivation. Could this have been caused by a connectome change? That's a good guess if we believe the connectionist mantra that the function of a neuron is chiefly defined by its connections with other neurons. In the 1990s Antonella Antonini and Michael Stryker
provided evidence pointing to the rewiring of axons bringing visual information into V1. Each incoming axon is monocular, meaning that it carries signals from just one eye. Depriving one eye caused its axons to retract dramatically, and the other eye's axons to grow. In effect, rewiring eliminated pathways from the deprived eye to V1, and created new pathways from the other eye to V1. This plausibly explained why Hubel and Wiesel had observed few V1 neurons responsive to the previously deprived eye.

Rewiring of V1 was important because it identified a connectome change that could be the cause of learning. Since rewiring both created and eliminated synapses and pathways, it served as another counterexample to the neo-phrenological idea that learning is simply the creation of synapses.

Antonini and Stryker were also able to address another question: Why is the brain less malleable after the critical period? Hubel and Wiesel had shown that monocular deprivation induced V1 changes in young kittens but not in adults. Once induced, the changes were reversible while the kittens were young, but became irreversible in adulthood. Antonini and Stryker explained this by showing that monocular deprivation in adulthood did not rewire V1. Furthermore, rewiring induced during the critical period was reversible if monocular deprivation was ended early,
but not if it was ended late.

Antonini and Stryker's research would seem to support the case for early intervention, as recommended by the zero-to-three movement. But an important pitfall of this argument has been pointed out by William Greenough, who discovered the increases in neural connections produced by environmental enrichment in rat brains. Amblyopia, like Genie's lonely upbringing,
deprived
children of normal experiences. It suggested the existence of a critical period for deprivation. Does it necessarily follow that there is also a critical period for enriching childhood with special experiences?

Greenough and his colleagues
say it doesn't. Since experiences like visual stimulation and exposure to language were normally available to all children throughout human history, brain development “expects” to encounter them, and has evolved to rely heavily upon them. On the other hand, experiences like reading books were not available to our ancient ancestors. Brain development could not have evolved to depend upon them. That's why adults can still learn to read, even if they did not have the opportunity in childhood.

What the zero-to-three movement really needs is an example of a critical period for learning from
altered
experience—an example that goes beyond mere deprivation. One such experiment was pioneered in 1897 by the American psychologist George Stratton.
He fastened a homemade telescope to his face and placed opaque materials around the eyepiece so that no other light could enter his eyes. The telescope was designed not to magnify images but to invert them. It turned the world upside down and also reversed left and right like a mirror. Stratton heroically wore the telescope twelve hours a day and blindfolded himself when he took it off.

As you can well imagine, Stratton was extremely disoriented at first, even nauseated. His vision conflicted with his movements. If he tried to reach for an object to his side, he would use the wrong hand. When he corrected himself and used the other hand, even the simple act of pouring milk into a glass was exhausting. His vision also conflicted with his hearing: “As I sat in the garden, a friend who was talking with me began to throw some pebbles into the distance to one side of my actual view. The sound of the stones striking the ground came, oddly enough, from the opposite direction from that in which I had seen them pass out of my sight, and from which I involuntarily expected to catch the sound.” But by the time Stratton ended the experiment, on the eighth day, he was moving with greater ease, and his vision and hearing had harmonized: “The fire, for instance, sputtered where I saw it. The tapping of my pencil on the arm of my chair seemed without question to issue from the visible pencil.”

What Stratton had discovered is that the brain can recalibrate vision, hearing, and movement to resolve conflicts between them. Eye surgeons have encountered a similar recalibration in patients with strabismus. This condition, more commonly known as “crossed eyes,” is sometimes corrected by surgery on eye muscles to rotate the eye. Turning the eye in this manner changes the vision of the patients, effectively rotating the world around them. The rotation is revealed by a simple experiment, in which patients are requested to point in the direction of a visual target while not being allowed to see their pointing arm.
They consistently point to one side of the target, because their movements now conflict with their changed vision. But if they are tested again a few days after surgery, the pointing errors are reduced, showing that the brain is recalibrating.

What happens in the brains of patients as they adapt to strabismus surgery? Starting in the 1980s, Eric Knudsen and his collaborators addressed this question with experiments on barn owls. They used special eyeglasses that rotated the world 23 degrees to the right by bending light rays to one side. This mimicked the rotation of the visual world produced by strabismus surgery. (In fact, similar eyeglasses are sometimes used as a treatment for severe strabismus.) Owls raised with these eyeglasses behaved in a way that looked skewed to an observer. If they heard a sound, they turned their heads to the right of the source. This skewed behavior
enabled them to look at the source, as it compensated for the rotation caused by the eyeglasses.

To study the neural basis of this behavioral change, Knudsen and his collaborators examined the inferior colliculus. This part of the brain is important for computing the direction of a sound based on comparing signals from the left and right ears. Much as there is a map of the body in Brodmann areas 3 and 4 (the sensory and motor “homunculi”), there is a map of the external world in the inferior colliculus. By recording spikes from neurons in this structure, Knudsen and his collaborators showed that the inferior colliculus map was displaced in a direction consistent with the skewed-looking behavior. They also showed that incoming axons shifted over in the map, suggesting that remapping had been caused by rewiring.

Knudsen and his collaborators further demonstrated a critical period for learning by applying and removing the eyeglasses at different ages. Placing the eyeglasses on adult owls raised normally did not produce a change in looking behavior. If young owls were raised with eyeglasses, the effects were reversible if the eyeglasses were removed early but not if removed in adulthood.

Based on the examples of the inferior colliculus and V1, it seems we can deny the possibility of rewiring in the adult brain. This might explain why adults have greater difficulty adapting to change. I mentioned in Chapter 2 that adults do not recover from hemispherectomy as well as children do. More generally, the Kennard Principle
states that the earlier the brain damage, the greater the recovery of function. This principle has been criticized as simplistic, since exceptions are well-known,
but it has some element of truth. It follows from rewiring denial, because rewiring is an important mechanism for remapping.

At the same time, the doctrine of rewiring denial is still under attack. Researchers using microscopes to monitor axons over long time periods in living brains have shown that new branches can grow
in adults. The experiments are controversial, but there is a growing consensus that at least short growths are possible, though long extensions might not be. Some suspect that such rewiring is responsible for the cortical remapping that accompanies phantom limbs, although there is still little conclusive evidence.

Other researchers are challenging the concept of the critical period, saying that the effects of early deprivation may be more reversible than was previously thought. The conventional wisdom has been that it's impossible to acquire stereo vision in adulthood. In her book
Fixing My Gaze,
the neuroscientist Susan Barry relates how she acquired some stereo vision in her forties, after a lifetime of stereo blindness
caused by childhood strabismus. She was able to do this by subjecting herself to a special regimen that trained her vision.

Barry's success suggests that the effects of critical-period experience are only difficult, not impossible, to reverse. Antonini and Stryker seemed to demonstrate convincingly that V1 lost its potential for change in adulthood, because rewiring ceased. This seemingly open-and-shut case has recently been challenged by the discovery of several treatments that restore plasticity to adult V1. Researchers have employed
four weeks of the antidepressant medication fluoxetine (better known by the trade name Prozac), pretreatment with ten days of darkness, or simple environmental enrichment in the style of Rosenzweig. These treatments appear to extend the critical period into adulthood or eliminate it altogether.

Knudsen and his collaborators initially emphasized the failure of adult owls to adjust to rotation of the visual world. But later experiments sent a more optimistic message.
The owls wore a sequence of eyeglasses, each of which rotated the world by a progressively larger angle. Over time, the owls eventually adapted to the same 23-degree rotation that the young owls could handle in one giant adjustment. The finding supported the general idea that adults can learn as much as juveniles, if training is done correctly.

Optimism about adult brain plasticity is currently in vogue. In the 1990s the zero-to-three movement contrasted the rigidity of the adult brain with the flexibility of the infant brain. Now the pendulum has swung to the other extreme. In his book
The Brain That Changes Itself: Stories of Personal Triumph from the Frontiers of Brain Science,
Norman Doidge tells inspiring stories about adults who have managed amazing recoveries from neurological problems. He argues that the brain is exceedingly plastic, much more than neuroscientists and physicians ever thought.

Of course the truth lies somewhere in between. It's incorrect to flatly deny the possibility of adult rewiring, but such denials might hold water if they were qualified with conditions. For example, they could be restricted to specific types of branches growing from certain neurons toward others, or from certain regions to others. And it's simplistic to regard rewiring as a single phenomenon. Rewiring actually encompasses a large number of processes involved in the growth and retraction of neurites. A more refined denial of rewiring might focus on just one of the processes included in this catchall term.

Since denials are conditional rather than absolute, they might be sidestepped by the right kind of training program, as Knudsen showed. And it appears that brain injury facilitates rewiring
by releasing axonal growth mechanisms that are normally suppressed by certain molecules. Future drug therapies might target these molecules, enabling the brain to rewire in ways that are not currently possible.

Because of our crude experimental techniques, only drastic kinds of rewiring have been detectable. That's why neuroscientists resorted to the rather extreme experiences of monocular deprivation and Stratton-type eyeglasses. The still-invisible, subtler kinds of rewiring
could well be important for more normal types of learning. Simply by providing a clearer picture of the phenomenon, connectomics is bound to aid research in this area.

 

In 1999 a bitter fight erupted between two neuroscientists. In one corner stood the defending champion, Pasko Rakic of Yale University. Starting in the 1970s, his famous papers had firmly established a dogma: No new neurons
are added to the mammalian brain after birth, or at least after puberty. The upstart was Elizabeth Gould
of Princeton University, who had astounded her colleagues by reporting new neurons in the neocortex of adult monkeys. (Most of the cerebral cortex consists of neocortex, the part mapped by Brodmann.) Her discovery was hailed by the
New York Times
as the “most startling”
of the decade.

It's not hard to understand why this face-off between two professors ended up on the front page. It's amazing when the body repairs itself. Skin wounds heal, leaving only a scar. Of all the internal organs, the liver is the champion at self-repair,
growing back even if two-thirds of it has been removed. If the adult neocortex could add new neurons, that would mean the brain has more capacity to heal itself than anyone expected.

In the end, neither contender could be declared the undisputed champion. The “no new neurons” dogma prevailed in the neocortex.
However, Rakic himself was forced to concede that neurons are continually added to two regions of the adult brain, the hippocampus and the olfactory bulb.
(The olfactory bulb is for the nose what the retina is for the eye, and the hippocampus is a major non-neocortical part of the cortex.)

Since new neurons normally appear in these two regions, even in the absence of injury, they presumably aren't for healing. Perhaps they enhance learning potential, much as new synapses were hypothesized to increase memory capacity by adding potential to learn new associations. The hippocampus belongs to the medial temporal lobe, in which the Jennifer Aniston neuron was found. Some researchers believe that the hippocampus serves as the “gateway” to memory;
they theorize that it stores information first and later transfers it to other regions like the neocortex. If this is the case, the hippocampus might need to be extremely plastic, and new neurons would endow it with extra plasticity. Similarly, the olfactory bulb might use new neurons to help store memories of smells.