Plasticity of the Mammalian Cortex

The notion that the adult brain is quite hard-wired goes back at least a century. Santiago Ramón y Cajal, the great Spanish neu-roanatomist who many believe is the father of modern neuroscience, wrote in 1913 in the conclusion of his work on Degeneration and Regeneration of the Nervous System: "In adult centers the nerve paths are something fixed, ended, immutable." However, studies in several cortical areas indicate that significant modifications in cortical structure and function can occur in adults. A number of these relate to changes in response to cortical damage, but others are in response to more normal experiences. Clearly, we can learn and remember new things all our lives, and the cortex is involved in learning and memory, as we shall see. But for many decades this was thought to be a special exception, that most of the adult mammalian brain was "immutable" as Cajal suggested.

Hints that this view is not correct came first perhaps from psychological experiments, which showed that if you place ocular prisms on human beings so that the world they see is upside down, the subjects adapt within a few days and then respond to visual stimuli quite normally thereafter. When the prisms are removed, again the subjects compensate, usually very quickly (in about a day) and they again respond quite normally to visual stimuli.

This result is in stark contrast to experiments on frogs in which their optic nerves are first severed, and then the eyes rotated 180° in the head. In cold-blooded vertebrates, the optic nerve regenerates and the axons grow back to make synapses on the neurons they originally contacted. Following regeneration of the optic nerves, these animals responded exactly as if their visual world was upside down, which it was after their eyes were rotated. When feeding, they misdirected their movements by 180°: When a fly appeared in the upper right quadrant of their visual field, they reacted with a movement toward the lower left quadrant, and this aberrant behavior was permanent. The frogs never recovered from it. Thus, cold-blooded vertebrates do seem to have a much more hard-wired nervous system than mammals. Their nervous systems have other features distinct from those of mammals as well—for example, an ability to regenerate central nervous system axons. We shall return to this topic in the next chapter.

The psychological experiments using prisms on human subjects did not teach us anything about the underlying cortical mechanisms involved or even if their compensation was cortical in nature. The first evidence for structural modifications as a result of altered sensory input to the cortex came from studies carried out by Michael Merzenich and his colleagues at the University of California, San Francisco. Using monkeys, they studied how sensory input from the fingers is first processed and represented on the cortex. Somatosensory information, representing touch, pressure, temperature, and pain from all over the body surface, is first processed in the cortex along a cortical strip, called the primary somatosensory area, located just behind the primary motor area.

The surface of the body is represented on this area in an orderly and consistent way, although the body representation is not strictly proportional. This is shown in Figure 4.1, a drawing based on the studies of Wilder Penfield, a Canadian neurosurgeon who electrically stimulated the human brain during operations for epilepsy. When the primary somatosensory area was stimulated, the patients reported a sensory sensation from a specific part of the body. Those parts of the body where sensation is more acute have more nerve endings, which in turn occupy more cortical area. Thus, the face and hand take up more cortical area than other parts of the body. The same is true for the primary motor area; electrical stimuli there caused a particular part of the body to move. A greater area of the primary motor cortex is concerned with those parts of the body that we can move more precisely, such as the fingers and parts of the face like the lips, mouth, and jaw. Undoubtedly, this larger cortical representation relates to the greater dexterity and sensory acuity of the hands and face compared to other parts of the body.

FIGURE 4-1 The primary somatosensory and motor areas of the primate (human) cerebral cortex. The two drawings to the right show the body part associated with each area, as indicated. The body representations are not proportional; areas of the body where sensation is more acute or that exhibit finer movements (such as the hands and face) have greater cortical representation.

FIGURE 4-1 The primary somatosensory and motor areas of the primate (human) cerebral cortex. The two drawings to the right show the body part associated with each area, as indicated. The body representations are not proportional; areas of the body where sensation is more acute or that exhibit finer movements (such as the hands and face) have greater cortical representation.

These cortical representations are also termed topographic maps, and the fingers are mapped on the somatosensory cortex so that each provides sensory input to a specific region of the cortex. These regions are sequentially arranged as shown in Figure 4-2A.

By recording from individual neurons in the hand/finger region of the somatosensory cortex and determining which finger is giving a particular neuron its sensory input, Merzenich and his colleagues first found that monkeys vary substantially in how much representation their fingers have on the cortex. Some monkeys have more cortical representation for a particular finger or groups of fingers than others. But of more interest was their finding that if the sensory nerves coming from a finger are cut (called

FIGURE 4-2 A: Representation of the digits on the primary somatosensory area of the monkey cortex.

B: Reorganization of the cortex following severing of the sensory nerves coming from one finger (digit 3). Initially, the area of the cortex from the deafferentiated finger was silent, but with time the area received input from neurons coming from adjacent fingers. The remaining fingers then had an increased representation on the cortex.

FIGURE 4-2 A: Representation of the digits on the primary somatosensory area of the monkey cortex.

B: Reorganization of the cortex following severing of the sensory nerves coming from one finger (digit 3). Initially, the area of the cortex from the deafferentiated finger was silent, but with time the area received input from neurons coming from adjacent fingers. The remaining fingers then had an increased representation on the cortex.

deafferentation), or an entire finger was removed, the representation of the fingers on the cortex changed quite dramatically. Initially, when they recorded from neurons in the area that received input from the lost or deafferentated finger, the neurons were silent as shown in Figure 4-2B. Stimulation of any finger or part of the hand produced no activation in most of the neurons. The exceptions were some neurons on the edges of the area in question, which probably shared some innervation with adjacent fingers, although this input was normally silent (a topic to which we shall return).

With time, however, it was possible to activate all the neurons in the deafferentated part of the cortex by stimulating adja cent fingers or, in some cases, other parts of the hand. This took time—weeks, even months—but the adjacent fingers gradually increased their representation and filled in the silent area. The adjacent digits now had a larger representation on the cortex than before as shown in Figure 4-2B. The conclusion from these experiments seems inescapable: New synapses and, presumably, new neuronal branches, can be formed in the adult cortex.

A question arising from these experiments is how much reorganization can take place in the adult cortex following deafferen-tation or loss of a part of the body. In the experiments involving the loss of a finger, the filling in of the silent cortex was relatively limited—it represented alterations in just 1-2 mm of cortex. In more extensive deafferentation experiments, carried out in monkeys by other investigators for a different purpose, the innervation to the cortex from an entire limb was cut. Eventually (the recordings were not made until 12 years after the deafferentation) the entire hand-arm region of the somatosensory cortex filled in, a distance of 10-14 mm along the cortex. Adjacent to the handarm region on the somatosensory cortex is innervation from the face as shown in Figure 4-1, and stimulation of the face, especially the lower jaw and chin, now activated neurons from the deafferentated area. Exactly how long it took for this reorganization of the somatosensory cortex to take place is not clear. As noted, the recordings were not made for more than a decade following the deafferentation.

Experiments by Vilayamur Ramachandran of the University of California in San Diego suggest a similar reorganization of the cortex in humans who have had a limb amputated. If the face of an arm amputee is touched lightly with a piece of cotton, the subject reports a sensation of the amputated hand being touched. Indeed, a crude representation of the hand is found on the face as shown in Figure 4-3.

Touching the cheek induces a sensation of the thumb being touched; the upper lip, stimulation of the index finger; and below the lips, touching of the little finger. It is likely that the face area has expanded into the limb area on the cortex. That the subject

FIGURE 4-3 If the face of an individual who has lost an arm is touched lightly with cotton, the individual often reports the sensation of the missing hand being touched. The face of such individuals carries a crude sensory representation of the hand.

experiences limb sensations following light touching of the face is of enormous interest. It has been proposed that this might relate to "phantom pain," in which amputees describe sensations and even pain from amputated limbs.

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