Epilepsy is a brain disorder characterized by periodic and unpredictable seizures
mediated by the rhythmic firing of large groups of neurons. It seems likely that
abnormal activity generates plastic changes in cortical circuitry that are critical
to the pathogenesis of the disease.
Brain Plasticity: What Is It?
What is brain plasticity?
Does it mean that our brains are made of plastic?
Of course not.
Plasticity, or neuroplasticity, describes how experiences reorganize neural pathways in the brain. Long lasting functional changes in the brain occur when we learn new things or memorize new information. These changes in neural connections are what we call neuroplasticity.
To illustrate the concept of plasticity, imagine the film of a camera. Pretend that the film represents your brain. Now imagine using the camera to take a picture of a tree. When a picture is taken, the film is exposed to new information — that of the image of a tree. In order for the image to be retained, the film must react to the light and “change” to record the image of the tree. Similarly, in order for new knowledge to be retained in memory, changes in the brain representing the new knowledge must occur.
To illustrate plasticity in another way, imagine making an impression of a coin in a lump of clay. In order for the impression of the coin to appear in the clay, changes must occur in the clay — the shape of the clay changes as the coin is pressed into the clay. Similarly, the neural circuitry in the brain must reorganize in response to experience or sensory stimulation.
- Neuroplasticity includes several different processes that take place throughout a lifetime – Neuroplasticity does not consist of a single type of morphological change, but rather includes several different processes that occur throughout an individual’s lifetime. Many types of brain cells are involved in neuroplasticity, including neurons, glia, and vascular cells.
- Neuroplasticity has a clear age-dependent determinant – Although plasticity occurs over an individual’s lifetime, different types of plasticity dominate during certain periods of one’s life and are less prevalent during other periods.
- Neuroplasticity occurs in the brain under two primary conditions:1. During normal brain development when the immature brain first begins to process sensory information through adulthood (developmental plasticity and plasticity of learning and memory).2. As an adaptive mechanism to compensate for lost function and/or to maximize remaining functions in the event of brain injury.
- The environment plays a key role in influencing plasticity – In addition to genetic factors, the brain is shaped by the characteristics of a person’s environment and by the actions of that same person.
Developmental Plasticity: Synaptic Pruning
Gopnick et al. (1999)[Gopnic, A., Meltzoff, A., Kuhl, P. (1999). The Scientist in the Crib: What Early Learning Tells Us About the Mind, New York, NY: HarperCollins Publishers.] describe neurons as growing telephone wires that communicate with one another. Following birth, the brain of a newborn is flooded with information from the baby’s sense organs. This sensory information must somehow make it back to the brain where it can be processed. To do so, nerve cells must make connections with one another, transmitting the impulses to the brain. Continuing with the telephone wire analogy, like the basic telephone trunk lines strung between cities, the newborn’s genes instruct the “pathway” to the correct area of the brain from a particular nerve cell. For example, nerve cells in the retina of the eye send impulses to the primary visual area in the occipital lobe of the brain and not to the area of language production (Wernicke’s area) in the left posterior temporal lobe. The basic trunk lines have been established, but the specific connections from one house to another require additional signals.
Over the first few years of life, the brain grows rapidly. As each neuron matures, it sends out multiple branches (axons, which send information out, and dendrites, which take in information), increasing the number of synaptic contacts and laying the specific connections from house to house, or in the case of the brain, from neuron to neuron. At birth, each neuron in the cerebral cortex has approximately 2,500 synapses. By the time an infant is two or three years old, the number of synapses is approximately 15,000 synapses per neuron (Gopnick, et al., 1999). This amount is about twice that of the average adult brain. As we age, old connections are deleted through a process called synaptic pruning.
Synaptic pruning eliminates weaker synaptic contacts while stronger connections are kept and strengthened. Experience determines which connections will be strengthened and which will be pruned; connections that have been activated most frequently are preserved. Neurons must have a purpose to survive. Without a purpose, neurons die through a process called apoptosis in which neurons that do not receive or transmit information become damaged and die. Ineffective or weak connections are “pruned” in much the same way a gardener would prune a tree or bush, giving the plant the desired shape. It is plasticity that enables the process of developing and pruning connections, allowing the brain to adapt itself to its environment.
Plasticity of Learning and Memory
It was once believed that as we aged, the brain’s networks became fixed. In the past two decades, however, an enormous amount of research has revealed that the brain never stops changing and adjusting.
Learning, as defined by Tortora and Grabowski (1996)[Tortora, G. and Grabowski, S. (1996). Principles of Anatomy and Physiology. (8th ed.), New York: HarperCollins College Publishers.], is the ability to acquire new knowledge or skills through instruction or experience.
Memory is the process by which that knowledge is retained over time.
The capacity of the brain to change with learning is plasticity.
So how does the brain change with learning?
According to Drubach (2000)[Drubach, D. (2000). The Brain Explained, Upper Saddle River, NJ: Prentice-Hall, Inc.], there appear to be at least two types of modifications that occur in the brain with learning:
- A change in the internal structure of the neurons, the most notable being in the area of synapses.
- An increase in the number of synapses between neurons.
Initially, newly learned data are “stored” in short-term memory, which is a temporary ability to recall a few pieces of information. Some evidence supports the concept that short-term memory depends upon electrical and chemical events in the brain as opposed to structural changes such as the formation of new synapses. One theory of short-term memory states that memories may be caused by “reverberating” neuronal circuits — that is, an incoming nerve impulse stimulates the first neuron which stimulates the second, and so on, with branches from the second neuron synapsing with the first. After a period of time, information may be moved into a more permanent type of memory, long-term memory, which is the result of anatomical or biochemical changes that occur in the brain (Tortora and Grabowski, 1996)[Tortora, G. and Grabowski, S. (1996). Principles of Anatomy and Physiology. (8th ed.), New York: HarperCollins College Publishers.]
Injury-induced Plasticity: Plasticity and Brain Repair
During brain repair following injury, plastic changes are geared towards maximizing function in spite of the damaged brain. In studies involving rats in which one area of the brain was damaged, brain cells surrounding the damaged area underwent changes in their function and shape that allowed them to take on the functions of the damaged cells. Although this phenomenon has not been widely studied in humans, data indicate that similar (though less effective) changes occur in human brains following injury. Kindly read Why Home Education of a Child is Very Important- Even Kindergarten is Late!
The importance of neuronal plasticity in epilepsy is indicated most clearly by an animal model of seizure production called kindling. To induce kindling, a stimulating electrode is implanted in the brain, often in the amygdala (a component of the limbic system that makes and receives connections with the cortex, thalamus, and other limbic structures, including the hippocampus; amygdala came from the latin-greek word, meaning almond, which describe the almond-like structure found in the brain ); Shown in research to perform a primary role in the processing of memory, decision-making, and emotional reactions, the amygdalae are considered part of the limbic system.
- It can be found easily in mammals under the rhinal fissure and closely related to the lateral olfactory tract. This almond like structure, ranging from 1-4cm , average about 1.8cm, has extensive connection with the brain.
At the beginning of such an experiment, weak electrical stimulation, in the form of a low-amplitude train of electrical pulses, has no discernible effect on the animal’s behaviour or on the pattern of electrical activity in the brain (laboratory rats or mice have typically been used for such studies). As this weak stimulation is repeated once a day for several weeks, it begins to produce behavioural and electrical indications of seizures. By the end of the experiment, the same weak stimulus that initially had no effect now causes full-blown seizures. This phenomenon is essentially permanent; even after an interval of a year, the same weak stimulus will again trigger a seizure. Thus, repetitive weak activation produces long-lasting changes in the excitability of the brain that time cannot reverse. The word kindling is therefore quite appropriate: A single match can start a devastating fire.
The changes in the electrical patterns of brain activity detected in kindled animals resemble those in human epilepsy. The behavioural manifestations of epileptic seizures in human patients range from mild twitching of an extremity, to loss of consciousness and uncontrollable convulsions. Although many highly accomplished people have suffered from epilepsy (Alexander the Great, Julius Caesar, Napoleon, Dostoyevsky, and Van Gogh, to name a few), seizures of sufficient intensity and frequency can obviously interfere with many aspects of daily life. Moreover, uncontrolled convulsions can lead to excitotoxicity.
Up to 1% of the population is afflicted, making epilepsy one of the most common neurological problems.
Modern thinking about the causes (and possible cures) of epilepsy has focussed on where seizures originate and the mechanisms that make the affected region hyperexcitable.
Most of the evidence suggests that abnormal activity in small areas of the cerebral cortex (called foci) provide the triggers for a seizure that then spreads to other synaptically connected regions. For example, a seizure originating in the thumb area of the right motor cortex will first be evident as uncontrolled movement of the left thumb that subsequently extends to other more proximal limb muscles, whereas a seizure originating in the visual association cortex of the right hemisphere may be heralded by complex hallucinations in the left visual field. The behavioural manifestations of seizures therefore provide important clues for the neurologist seeking to pinpoint the abnormal region of cerebral cortex. Epileptic seizures can be caused by a variety of acquired or congenital factors, including cortical damage from trauma, stroke, tumors, congenital cortical dysgenesis (failure of the cortex to grow properly), and congenital vascular malformations. One rare form of epilepsy, Rasmussen’s encephalitis, is an autoimmune disease that arises when the immune system attacks the brain, using both humoral (i.e. antibodies) and cellular (lymphocytes and macrophages) agents that can destroy neurons. Some forms of epilepsy are heritable, and more than a dozen distinct genes have been demonstrated to underlie unusual types of epilepsy. However, most forms of familial epilepsy (such as juvenile myoclonic epilepsy and petit mal epilepsy) are caused by the simultaneous inheritance of more than one mutant gene.
No effective prevention or cure exists for epilepsy. Pharmacological therapies that successfully inhibit seizures are based on two general strategies.
One approach is to enhance the function of inhibitory synapses that use the neurotransmitter GABA;[Gamma-Aminobutyric acid(γ-Aminobutyric acid); (also called GABA for short) is the chief inhibitory neurotransmitter in the mammalian central nervous system. It plays the principal role in reducing neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone.] the other is to limit action potential firing by acting on voltage-gated Na+ channels. Commonly used antiseizure medications include carbamazepine, phenobarbital, phenytoin (Dilantin®), and valproic acid.
These agents, which must be taken daily, successfully inhibit seizures in 60–70% of patients. In a small fraction of patients, the epileptogenic region can be surgically excised. In extreme cases, physicians resort to cutting the corpus callosum to prevent the spread of seizures (most of the “split-brain” subjects were patients suffering from intractable epilepsy).
One of the major reasons for controlling epileptic activity is to prevent the more permanent plastic changes that would ensue as a consequence of abnormal and excessive neural activity.
- THE CORPUS CALLOSUM
The corpus callosum (Latin for “tough body”) is by far the largest bundle of nerve fibers in the entire nervous system. Its population has been estimated at 200 million axons—the true number is probably higher, as this estimate was based on light microscopy rather than on electron microscopy—
a number to be contrasted to 1.5 million for each optic nerve and 32,000 for the auditory nerve. Its cross-sectional area is about 700 square millimeters, compared with a few square millimeters for the optic nerve. It joins the two cerebral hemispheres, along with a relatively tiny fascicle of fibers called the anterior commissure, as shown. The word commissure signifies a set of fibers connecting two homologous neural structures on opposite sides of the brain or spinal cord; thus the corpus callosum is sometimes called the great cerebral commissure.
Until about 1950 the function of the corpus callosum was a complete mystery. On rare occasions, the corpus callosum in humans is absent at birth, in a condition called agenesis of the corpus callosum. Occasionally it may be completely or partially cut by the neurosurgeon, either to treat epilepsy (thus preventing epileptic discharges that begin in one hemisphere from spreading to the other) or to make it possible to reach a very deep tumor, such as one in the pituitary gland, from above. In none of these cases had neurologists and psychiatrists found any deficiency; someone had even suggested (perhaps not seriously) that the sole function of the corpus callosum was to hold the two cerebral hemispheres together. Until the 1950s we knew little about the detailed connections of the corpus callosum. It clearly connected the two cerebral hemispheres, and on the basis of rather crude neurophysiology it was thought to join precisely corresponding cortical areas on the two sides. Even cells in the striate cortex were assumed to send axons into the corpus callosum to terminate in the exactly corresponding part of the striate cortex on the opposite side.
In 1955 Ronald Myers, a graduate student studying under psychologist Roger Sperry (Roger Wolcott Sperry) at the University of Chicago, did the first experiment that revealed a function for this immense bundle of fibers. Myers trained cats in a box containing two side-by-side screens onto which he could project images, for example a circle onto one screen and a square onto the other. He taught a cat to press its nose against the screen with the circle, in preference to the one with the square, by rewarding correct responses with food and punishing mistakes mildly by sounding an unpleasantly loud buzzer and pulling the cat back from the screen gently but firmly. By this method the cat could be brought to a fairly consistent performance in a few thousand trials. (Cats learn slowly; a pigeon will learn a similar task in tens to hundreds of trials, and we humans can learn simply by being told. This seems a bit odd, given that a cat’s brain is many times the size of a pigeon’s. So much for the sizes of brains.)
Not surprisingly, Myers’ cats could master such a task just as fast if one eye was closed by a mask. Again not surprisingly, if a task such as choosing a triangle or a square was learned with the left eye alone and then tested with the right eye alone, performance was just as good. This seems not particularly impressive, since we too can easily do such a task. The reason it is easy must be related to the anatomy. Each hemisphere receives input from both eyes, a large proportion of cells in area 17 receive input from both eyes. Myers now made things more interesting by surgically cutting the optic chiasm in half, by a fore-and-aft cut in the midline, thus severing the crossing fibers but leaving the uncrossed ones intact—a procedure that takes some surgical skill. Thus the left eye was attached only to the left hemisphere and the right eye to the right hemisphere. The idea now was to teach the cat through the left eye and test it with the right eye: if it performed correctly, the information necessarily would have crossed from the left hemisphere to the right through the only route known, the corpus callosum. Myers did the experiment: he cut the chiasm longitudinally, trained the cat through one eye, and tested it through the other—and the cat still succeeded. Finally, he repeated the experiment in an animal whose chiasm and corpus callosum had both been surgically divided. The cat now failed. Thus he established, at long last, that the callosum actually could do something—although we would hardly suppose that its sole purpose was to allow the few people or animals with divided optic chiasms to perform with one eye after learning a task with the other.[Source: David Hubel’s-Eye, Brain And Vision]
The Corpus Callosum Defined
Imagine for a moment two people who think and behave in very similar ways yet perceive the world a bit differently from one another.
What if they could share their thoughts, then modify them into a single world view based on both perceptions?
This may seem weird, but our brain works this way thanks to the corpus callosum.
Located near the center of the brain, this structure is the largest bundle of nerve fibers that connects the left and right cerebral hemispheres, much like a bridge. Traffic flows in both directions, but instead of vehicles travelling over the gap, it is information.
Split Brain Patients
Until the early 1950s, the function of the corpus callosum had alluded scientists. No one knew what it did, except to connect the two cerebral hemispheres. By the 1960s, scientists at least knew that nerve fibers within the callosum connected corresponding areas in the two hemispheres but did not yet understand the complexity involved. However, this limited knowledge was used in an attempt to help patients who suffered from severe and constant seizures.
Normally, electrical activity in the brain flows down specific pathways. This is not so during seizures. The electrical charges could end up anywhere in the brain and stimulate the uncoordinated muscular activity that many people associate with a seizure. Roger Sperry was the scientist who developed a surgical procedure to cut the corpus callosum and stop the spread of this activity from one hemisphere to the other. This procedure was a last ditch effort to normalize the lives of seizure patients, and it was very effective. However, there were a few unexpected results.
After surgery, some patients exhibited contrary behaviours, such as pulling their pants on with one arm while simultaneously pulling them off with the other. Another patient began to shake his wife aggressively with his left hand as his right hand intervened to stop the attack. These results began a plethora of investigations which eventually lead to the understanding that each hemisphere tends to specialize in certain activities, i.e., speech (left side) or emotional reactivity (right side).
After the patient’s callosum was cut, the attack on his wife was instigated by the right hemisphere (via his left hand) because the left hemisphere (right hand) didn’t realize what was happening soon enough to prevent it. Such a conflict ordinarily would have been resolved in the patient’s brain before the external behaviour was produced.
To a greater or lesser degree, both hemispheres contribute to the initiation of a particular behaviour. It is the corpus callosum that provides the communication pathway to coordinate these activities and helps to incorporate them into daily life. Without this brain structure, we literally have two separate personalities in your head, each with its own agenda. [Source: Jay Mallonee – Jay is a wildlife biologist, college professor and writer. His master’s degree is in neurobiology and he has studied animal behaviour since 1976.]
- SCHEFFER, I. E. AND S. F. BERKOVIC (2003) The genetics of human epilepsy. Trends Pharm. Sci. 24: 428–433.
- ENGEL, J. JR. AND T. A. PEDLEY (1997) Epilepsy: A Comprehensive Textbook. Philadelphia: Lippincott-Raven Publishers.
- McNamara, J. O. (1999) Emerging insights into the genesis of epilepsy. Nature 399:
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