Science in Christian Perspective

Electrical Stimulation of the Nervous System for the Management of Neurological Disorders
CURTIS A. GLEASON
Nenrosciences Department
Mount Zion Hospital and Medical Center
San Francisco, California

From: JASA 28 (December 1976): 151-156.

The approach that this paper takes to the theme, "What is Man'?", is to look at man as a machine. By understanding the mechanistic characteristics, particularly of the nervous system, we can learn how to compensate for disorders related to the nervous system. With our increasing knowledge of neuroanatomy and neurophysinlngy and the advances in electronic technrilogy, we are understanding and practicing nondestructive approaches to the long-term management of these disorders.

A Long History

An electrical approach to pain management was used in Rome around 46 AD, according to medical historians. The agent was the black torpedo fish that was found along the shores of the Mediterranean Sea. The pain of gout was eliminated when the afflicted stood in a pool with these fish, and headache was relieved by the application of the fish to the head. More than 200 years ago in England, John Wesley, the founder of many social reforms including free clinics and founder of the Methodist Societies, used electrical stimulation as a "natural and easy method of curing most disorders". When his brother, Charles, was critically ill he sent the following instructions to a friend:

"1. Carry Dr. Whitchead to him, whether my brother consents or not;
2. get him outdoor exercise if possible;
3. let him he electrified-not shocked but filled with electric tire; and
4. inquire if he has made his will."

As long as people have been able to generate electricity it has been applied to people in an attempt to cure their ailments. John Wesley, as well as others, used the spinning discs of the electrostatic generator, at that time the most readily available source of electricity.

Later, around 1800, a new source of electricity became available. Volta discovered how to use two dissimilar metals to produce electricity, the beginning of the electric battery. At the same time, Galvani discovered what was later referred to as "intrinsic animal electricity" (in species other than the electric fish). Hence the discovery and significant realization that people might be running on electricity. Since that time there have been many examples of using electricity to alleviate the physical (and even mental) disorders of people. The extent to which electricity was used in medicine is seen in the book Electricity in Medicine, published in 1919. The authors, Jacoby and Jacoby, described a variety of methods of applying electricity to the body to cure just about every known human ailment. Electrification of the whole body was easily achieved by placing the electrodes of the electrical generator in the bath water, for example. However, not all procedures proved to be effective and soon the use of electricity as described by the Jacobys subsided. The continued use of electricity on people was limited primarily to muscle stimulation, diathermy and electrocoagulation.

However, studies of the effects of electrical stimulation continued, particularly with animal preparations. In 1956, researchers found that the reactions of animals to painful stimuli of the limbs were eliminated when the spinal cord was electrically stimulated. These experimenters were seeking an understanding of the physiological basis for pain and its control and proposed a theory that a "gate" mechanism in the spinal cord could account for their observations. Others investigated this theory and participated in the development of implantable electrical stimulators for the management of chronic pain. The implantable stimulator consisted of a small radio receiver that was attached to small wires that penetrated the spinal cord. The receiver was tuned to a special battery-powered transmitter, which the patient was able to control.

The sensation experienced by the patient is usually a tingling in the area of the pain. In general, about ten minutes of stimulation produced several hours of relief of a previously intractable chronic pain. However, not all patients responded favorably to the implanted system. Either the electrical stimulation was ineffective or the tingling sensation was too unpleasant. It became apparent that the patients should he screened to determine whether a stimulator should be implanted or not. To do this, electrodes (EKG patches) were placed on the skin over or near the painful areas and then connected to an external pulse generator. Most often it was found that this external application was sufficient to give pain relief while the stimulator was on. In addition, in some cases several hours of relief were obtained after a few minutes of stimulation. Hence, electrical stimulation on the skin for pain management was rediscovered. In contrast to the equipment that was used earlier in history, the modern pulse generators contain means for very carefully controlling the amount of current delivered. The controls for the amount of current used are available to the patient. The sensations on the skin are varied. Examples of sensations that have been reported are massage-like, vibrations, and pins and needles.

With the latest achievements in technology, including the miniaturization of electronic systems, sophisticated applications of electricity to the body can be effective for many neurological disorders.

Neuroanatomy and Neurophysiology

Nerve Cells-The nervous system is composed of specialized cellular units or nerve cells called neurons that are linked together by special junctions to form pathways for the nerve impulses. The longest neurons (single cells) extend from the toes to the brain stem. These cells make up the &ectrical circuits and produce the electricity that was discovered in the 1800's. Of course this is not the same form of electricity as that produced by the utility companies for heat and light. Although electricity is the movement of electric charges, utility company electricity is the movement of free electrons in a metallic conductor whereas body or nervous system electricity is produced by the ions of the chemicals in and around the nerve cells. Electrical impulses in a wire are produced by the electrons moving momentarily in one direction but electrical impulses in nerves are much more complex. A crude analogy would he the chemical change along a firecracker fuse after it is ignited. The nerve, however, recovers from its chemical changes and is able to propagate another impulse very soon after the preceding impulse. The electrical impulse in a wire travels instantaneously, for all practical purposes. In contrast, the nerve impulse travels quite slowly, about twenty meters in one second.

The nerve impulse can be initiated in a nonphysiological way by an electrical or a mechanical disturbance of the chemical or structural environment of the nerve cell. Some examples of uncontrolled stimulation of the nervous system are: striking the ulnar nerve in the elbow, which produces a sharp tingling sensation in the lower arm and hand, and sticking the fingers in an empty, energized lamp socket, which produces tingling in the fingers.
Nervous System-The nervous system, which contains billions of neurons, consists of the central nervous system and the peripheral nervous system. Certain specialized anatomical structures, namely the cerebrum, cerebellum, brain stem and spinal cord make up the central nervous system. The whole system can be divided also into the sensory and the motor systems. Both of these systems contain ascending and descending pathways, and they perform facilitatory and inhibitory functions.

Sensory System-The sensory system contains the general senses and the special senses. The general senses include temperature, pain (nociception), simple touch and stereogliosis. The special senses are vision, hearing, taste, smell and balance. There are many types of receptors in the body that respond each in a special way to a variety 0f stimuli. Some are sensitive to stimuli originating some distance away. Others are sensitive to stimuli affecting the skin, and others to stimuli originating within the body. However, perception or recognition of a sensation takes place only when the nerve impulses reach certain higher centers, such as the cerebral cortex. It follows, then, that disruption of any part of the system by disease or trauma would produce a sensory deficit.
The visual system includes the eyes, optic nerve, optic track, brain stem and the visual cortex of the cerebrum. Blindness can occur if any part of the system ceases to function properly. With the present stateof-the-art the visual system has not been replaced by electrical stimulation of any point along the visual system. People have reported "seeing" flashes of light during stimulation of the visual cortex, but meaningful patterns have not been elicited.
However, electrical stimulation has been used to enable blind people to sense the presence of objects. A large array of many small stimulating electrodes are placed on the surface of the skin, for example on the hack, and activated according to the patterns produced by images from a small television camera. A person without vision is able to learn the meaning of patterns of stimulation on the skin just as a person with vision learns the meaning of visual patterns. The dimension of color, however, is lost by this method.

Failure of any of the components of the auditory system affects the ability to hear. In this case stimulation of the auditory or associated pathways and cortex elicits noise. Tests are being carried out in several centers to determine effective ways by which sounds can be modulated or processed so that the electrical stimulation of the coehlear nerve, for example, can produce meaningful information.

The sensation of smell by stimulation of the olfactory bulbs has also been reported. The suppression of vertigo by stimulation of the vestibular system has not been reported. But vertigo has been elicited during electrical stimulation of the brain stem and the cerebellum. The neurological pathways for taste are quite deep in the brain stem and they would be difficult to sCmulate effectively in people, but presently there does not seem to he a need for eliciting taste by electrical stimulation.

As for the general senses, electrical stimulation at any point along the sensory system, from the skin to the cortex, has resulted in such sensations a tingling, warmth, vibrations and pain. The latter is sensed as the amplitude of the electrical pulses is increased higher than that required to elicit a tingling sensation. The sensation of pain, from a cut or abrasion of the skin for example, in the periphery is transmitted by nerve cells that are smaller in diameter than those transmitting other sensory information. As a result, electrical stimulation will initiate activity in the other sensory nerves at an amplitude lower than that required to elicit pain. Also, it has been found that some mechanism 

"We should never forget that it is not the electricity as such that cures, but that it is the entire procedure of electrization with all the physical and psychic effects thereby produced."

that blocks the information in the pain pathways to the brain when a great amount of activity is present in the other sensory nerves. Hence, low amplitude stimulation of the skin, peripheral or cord nerves can block the sensation of pain from a peripheral injury.

However, the sensation or perception of pain presumably is very complex and certainly not understood. A leg could he in pain as the result of a stroke. Electrical stimulation of the nerves from the leg will not provide any benefit because the pain is being generated in the brain, probably in the higher levels of the brain stem, but not in the leg. In this example it is easy to understand why such destructive procedures as cutting of peripheral and cord nerves would he ineffective in stopping the pain. However, the idea of destroying the brain center that perceived pain aroused some interest which resulted in the development of a special procedure and instrumentation that made it posishle to selectively destroy nerve cells in the bran stem. This procedure is discussed after a quick review of the motor system.

Motor System-A special area of the cerebral cortex is the site of the nerve cells that are used to initiate voluntary motor control. Some of these cells have very long axons that descend to the spinal cord while other cortical cells terminate in the brain stem. The spinal cord is the site of the cells (motor neurons) that directly activate the skeletal muscles. Activity of these cells causes the muscles to contract or relax in response to the information that comes from the brain stem and cerebral cortex. In between the anatomical extremes of the cortical cells and the spinal motor cells is a complex array of interconnections within and among the cerebrum, cerebellum, brain stem and cord that are required to perform purposeful movements.

The proper execution of voluntary movements depends on a properly functioning involuntary system, also. For example, simply raising an arm requires complex activity of the central nervous system. In addition to the muscles that contract to raise it, other muscles (antagonists) must relax. If one is standing, then leg and trunk muscles must respond to maintain posture and balance as the raising arm shifts the center of gravity. Also, when the arm is raised to a desired position, it is expected to reach that position without hunting and to remain steady. To achieve proper limb control, information on limb position and muscle tension is sent to the spinal cord, the brain stem and the cerebellum. The information in the cord is processed to assist in the relaxing of the antagonists as other muscles are contracting (prime movers) to effect coordinated synergistic movements. The cerebellum coordinates the action of muscle groups and times their contractions so that limb movements are performed smoothly and accurately. It is understood that the signals that leave the cerebellum are primarily inhibitory and tend to provide a braking action to the motor control circuits in the brain stem. The brain stem is reciprocally connected to the cerebrum, cerebellum and spinal cord and contains many groups of cells that are extensively interconnected. Some of these groups are facilitatory in their function and others are inhibitory. Our righting and antigravity reflexes are controlled by cell groups in the brain stem. The controls for the complex coordination of muscle groups for the swallowing reflex, for eye movements and for eye focusing are found in the brain stem. In addition, the primary control of blood pressure, cardiac activity, respiration and alimentary movements originate in the brain stem.

There are many clinical signs associated with disease or damage of the motor system depending on the location and extent of the lesion. Flaccid paralysis occurs when the motor neurons in the cord or the associated peripheral nerves are damaged thereby removing all control to the muscles. Damage to motor pathways in the cord or to structures in the brain stem associated with the motor system or to the motor cortex also pro duces paralysis of skeletal muscles. However, in this case, the motor neurons are activating the muscles but in an uncontrolled manner, hence producing spastic paralysis. This type of paralysis of the muscles is the most common clinical characteristic of cerebral palsy. Volitional control of the muscles is difficult due to the increased tension of the muscles because of the inability of the antagonists to relax.

A common disease that is associated with degeneration of certain parts of the brain stem is Parkinson's disease. The most obvious clinical sign is the tremor, which is caused by damage to a part of the involuntary muscle control system. The tremor is more pronounced during rest than during intended movements. There is also a lack of swing in the arms during walking, which itself is difficult to initiate but once in progress also is difficult to terminate.
Disease or damage to the cerebellum produces a number of characteristic signs involving the motor system. Some examples are intention tremor, which is evident during intended movements but not present during rest; disturbances of gait and posture; and inability to stop a movement at a desired point, that is, overshooting or undershooting.

Multiple sclerosis is usually a diffuse, chronic, slowly progressive neurologic disease that degenerates the white matter of the nervous system, resulting in the breakdown of the insulating qualities of the cell's long fibers. The resulting clinical signs of course depend upon the site and extent of the disease. Some common signs are intention tremor and spastic paralysis.

Stroke, or a cerebral vascular accident, can produce many neurological disorders if not death. Common signs are pain and spastic paralysis, either together or separate.

Epilepsy is characterized by sudden, transient alterations of brain function, usually with motor or sensory involvement and often accompanied by alterations in consciousness. It is the result of abnormally active brain cells caused by injury, infection, genetic factors or unknown factors. Increased nerve cell activity in the cerebrum can produce sensation of vision, sound, smell or uncontrolled muscle activity, or a combination of these depending on the extent of the abnormal activity.

Electrical Treatment of Motor System Disorders

The most obvious, and simplest, application of electrical stimulation is to the muscles of a paralyzed limb. Healthy muscles will contract either with direct stimulation or through intact nerves that attach to the muscle. Electrodes that are placed either on the surface of the skin or implanted on the nerve can be activated appropriately to produce purposeful movements. Spastic paralysis may also he approached by this technique. As an example, some victims of stroke are left with spastic paralysis of a foot, resulting in "foot drop", an extension of the foot due to the greater strength of the extensors than of the flexors. Electrical stimulation of the nerve going to the foot flexor muscles will increase the tension in those muscles but, because of the cord interneuronal connections, also will decrease the tension in the extensors. A switch in the heel of the shoe activates the electronics at the correct part of the walking cycle.

The cerebellum, which produces an overall inhibitory effect on the motor system, is also a logical candidate for the reduction of the overactive muscles in spastic paralysis. If the output of the cerebellum could be increased, then possibly the action of the motor system could be decreased. Hence, stimulation of the cerebellum was investigated and has been successful in reducing spasticity.

Intractable epilepsy, which does not respond to medication, is another candidate for electrical stimulation of the motor inhibitory system. An epileptic attack has been described as an electrical storm of the cerebral cortex because of the characteristics of the brain waves that are recorded during a seizure. The inhibitory output of the cerebellum was found to be effective in suppressing neuronal activity in the cerebral cortex. Hence, electrical stimulation of the cerebellum is being investigated for the control of epilepsy in people.

The discovery that electrical stimulation of the spinal cord could reduce spasticity was made when a patient with intractable chronic pain was being treated with electrical stimulation of the spinal cord. This person had muscle spasticity, too, resulting from multiple sclerosis. After a few sessions of cord stimulation it was noted that the spasticity as well as the pain was reduced.

Electrical stimulation of the phrenic nerve, which is involved in our breathing process, has also been effective. The nerve is stimulated automatically to produce periodic contractions of the diaphragm. This technique gives the person freedom of movement that is not available from an iron lung.

The victim of a broken back or neck can experience not only paralysis of the skeletal muscles but also of the bladder muscles. Bladder contraction has been effected by electrical stimulation either of the cord, near where the nerves leave it to go to the bladder, or of the bladder wall muscles directly.
An area in the brain stem that has been electrically stimulated enabled a partially paralyzed arm to respond to a desired movement, That is, when the patient tried to raise his arm he was unable to until the stimulator was turned on. If he did not try to raise his arm then it remained at rest even if the stimulator was turned on. The stimulation was effective only in augmenting volitional movement in this ease.

Stereotaxic Surgery

Even though certain areas or sites can be electrically stimulated to overcome certain neurological disorders, electrodes must be placed in the desired sites. In the simplest cases the electrodes are attached to peripheral nerves by relatively common surgical procedures. For placing electrodes in deep brain targets a stereotaxic surgical procedure is required. The first stereotaxic apparatus for reaching deep into the human brain was described in 1947. The stereotaxic procedure was developed for the purpose of placing a wire or small tube accurately into a desired suhcortical area with minimal injury to the cerebral cortex or to the white matter. The purpose of stereotaxic surgery was to produce lesions (by thermocoagulation) or to remove or inject fluids in deep brain structures.

The apparatus in use today consists of a light, rigid metal frame that contains millimeter scales on the three axes. Skull x-rays are taken with air or x-ray opaque dye injected into the brain and with the frame mounted on the skull. The scales on the frame provide the information that is needed to compute the coordinates of the desired brain targets in terms of the frame coordinate system. A standard brain atlas provides the relative coordinates of various deep brain structures. The skull x-rays show the relationship of the patient's brain landmarks and brain size with the scales of the attached frame. Computation of the frame coordinates of desired deep brain targets are based on the standard atlas coordinates of these targets. The apparatus is designed so that the tip of the electrode, which is attached to a long, one millimeter diameter tube, is always at the center of a sphere that is scribed by the electrode holder, which is attached to the frame. The electrode holder is attached to the frame so that the center of the sphere is at the x, y, and z coordinates that are determined for a particular target.

After electrode implantation, skull x-rays are used to verify the electrode placement. A few days after implantation, with the patient awake and alert, a laboratory pulse generator is attached to the electrode wires that are protruding through the scalp. Low amplitude electrical impulses are then used to provide a physiological test of the placement. As an example, an electrode placed in a motor facilitatory area will increase the tremor in a person with Parkinson's disease. A heat lesion that is made with this electrode would result in a reduction or elimination of the tremor. For pain it was found that electrical stimulation of pain perceiving areas reduced the sensation of pain, but also that destruction of tissue reduced the pain.

Although the motor and sensory systems are anatomically separate in the brain stem there is still the possibility of undesired side effects from lesions. For example, destruction of tissue to stop tremor might also produce a sensory deficit if the electrode were too close to the sensory fibers. Similarly, the sensation of pain could be reduced by destroying tissue, but an area of the involved limb or side could be left with either a chronic tingling sensation or a numbness. These possible side effects had to be considered in early stereotaxic surgery because the effects of a lesion are irreversible. Brain cells are unique cells in that they do not reproduce; once destroyed there is no replacement.

Because electrical stimulation of the deep electrodes was used to provide a physiological test of electrode placement, records were obtained of the effects of stimulation in the human brain. However, even though the results of the stimulation may have been beneficial, no means were available to permit continued periods of stimulation over long periods of time. In order to provide a means of chronic electrical stimulation of selected targets, electronic devices had to be designed for chronic implantation.

The suppression of chronic, intractable pain was the first use of the implantable systems. Then the investigation, in animals and humans, of chronic stimulation for other purposes became more intense. Now with the implantable hardware available and further knowledge of the human nervous system the possibility of nondestructive means for reducing the clinical manifestations of neurological disorders can be realized.

Summary

The recorded use of electricity for the management of certain neurological disorders dates back almost two thousand years. Now, new applications of electrical stimulation are possible with the development of miniaturized electronic hardware and with increased understanding of the nervous system. Special characteristics of nerve cells permit their activation by electrical stimulation. In addition, the anatomical separation of the sensory and motor systems as well as separate facilitatory and inhibitory centers permit selective control of certain neurological processes. Sensory modalities can be augmented and muscle contractions can be initiated or suppressed to compensate for certain neurological disabilities. The stereotaxic procedure, which allows the placement of electrodes into selected deep brain targets, and the development of sophisticated electronic stimulating systems provide a minimal destruction of the nervous system and therefore offer new possibilities for the management of neurological disorders in people.

In their book, Electricity in Medicine, 1919, Jacoby and Jacoby list seven rules that should he followed when applying electricity to people. The rules point out the usual precautions that should be followed when using electricity, for example, the first rule is ". . . turn off the power before applying the electrodes". However, I think that the seventh rule is most appropriate. Perhaps it provides us with a better understanding of how electricity cures our ailments. Their seventh rule is, "We should never forget that it is not the electricity as such that cures, but that it is the entire procedure of electrization with all the physical and psychic effects thereby produced".

REFERENCES

Historical and General:
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Sensory Systems:
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Motor Systems:
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