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INSIDE THE NEURON: Part III
If axons are great cytoplasmic elongations, dendrites , taken from the Greek dendron for tree, are just like branchings and rebranchings of trees that are closer to the cell body and nucleus. Dendrites communicate electrically with the cell body. The dendritic input is from other cells, often from thousands of axons that transmit through them to the cell that at any instant correlates these thousands of inputs and decides whether or not to fire. Or, failing to fire the neuron reaches a certain level of excitation and functions as a communication device. The pictures or some types of neurons illustrate the critical link of form and function.. The best example is the large neuron within the cerebellum the Purkinje cell. This cell that lines the folia or cerebellar convolutions, receives input from thousands of synapses over its elaborate dendritic structure but also along over its axon. All of that input, some of it excitatory, some inhibitory, is integrated. The final output of the Purkinje cell axon is inhibitory or controlling. What does the cell control? Fluid and precise movements, fine hand movements and balance as of a ballet dancer, illustrating how wrong it is, how far off one must be to consider this complex executive merely as an "on' or "off" state at a given moment in mathematical representations. Each Purkinje cell is an executive.
Figure 1: Shapes of neurons.
Drawn by Deiters and Cajal. To give some idea of the variety of shapes and
function of cells[1].
A large portion of a neuron's function is determined by its shape. Consider the tens of thousands of branchings that make up its dendritic system. Also the typically long axon that may be over a yard in length. The architecture or the cell determines just how information will flow through it and to other cells in this vast machine. While there are exceptions, the information flow is generally from dendrite to cell body to axon.
The overall structure of the neuron can't be left to chance, for the neuron is in the business of establishing contacts. It is a social type of cell that never works in isolation. The significance of the cell's specific shape is that some synapses lie closer, some farther from the center of the cell. Given thousands of inputs, some will have more, some, less influence on the decision for the neuron, whether or not to fire. The single synapse has ordinarily, very little influence on this decision. At any given instant, the sum total of influences determine what the neuron will do. These are summated spacially, that is some synapses are closer, some further from the central sphere of influences, the inner circle, and temporally, there is the sum of inhibitory synapses and excitatory ones affecting the decision of the neuron over time. With transmission across a synapse the effect on the cell will be felt only for a finite amount of time, then if it is without influence the effect will cease. The overall sum of synaptic influences determines the degree of excitation of the cell, especially its state of polarization, whether depolarized or hyperpolarized.
Other synapses are on the axon of the cell and their influence is different. Some, that are close to the release of neurotransmitter laden vesicles, no longer affect the action potential but modulate the number of vesicles should the cell fire. Some of these synapses modulate the amount of transmitter released in cells which release transmitter without firing. Synapses structurally then are of many types, axo-dendritic, perhaps the most common type, axon to cell body and axo-axonal, dendo-dendritic.
Cytoskeletal proteins in part help to form the nervous system and maintain the structure of nerve cells so important to the neuron's gregarious nature. The neuron is the only cell whose cell body is stretched so as to provide connections with fellow neurons. It does not function as an isolated executive, but lives, much as a whole person does, as part of a complex network with its neighbors.
Electrical impulses need to travel considerable distances in the central and peripheral nervous systems. The CNS has its own myelin on axons formed by oligodendroglia whereas peripheral nerves have their own chemically distinct myelin made by Schwann cells. Myelin is a fatty insulator blocking the egress and ingress of ions over the long axon. The larger the diameter of the axon, with its thick myelin, the faster is the conduction. Touch receptors depend on thick axons with myelin, whereas pain fibers are unmyelinated or lightly myelinated, hence conducting information slowly.
In the myelin covered zones Sodium, Potassium and other ions are unable to pass through and an electric charge is felt over these zones, instantaneously creating an electric field spreading over the volume of the axon over a short distance. When an action potential invades the axon covered with myelin there is a fairly pronounced alteration of charge that goes instantaneously over a distance in the axon. However over the myelin covered area that electrical difference cannot result in any flow of ions across the cell membrane. This must occur only in the denuded uncovered node of Ranvier. As soon as the field is felt in the nodal area Sodium rushes in and there are other ionic changes similar to those described above with neuron excitation. Again, there is the spread passively (electrotonically) of a field of electrical charge influencing the next node which will in its turn respond with its own flux of ions. The passive electrotonic spread of charge in the internodal (covered) area is almost instantaneous and to the extent that it is possible for electric currents to travel in this way, transmission will be very fast. This can only be achieved over a very short length of axon before the spread of electrical charge degrades and will no longer be a factor. The nodal denuded zone serves to recharge the battery to create another area of electrotonic spread.
Axons also function without myelin, but in that case electrical conduction is comparatively slow. Take away myelin from an axon and you may even find its conduction completely blocked. If the diameter of the axon is larger one can make up for some of this lack of speed because a larger diameter will conduct impulses faster. This is the strategy employed by invertebrates such as the squid which has some "giant" axons studied intensively in the past because of their accessibility and sheer size. Larger diameter axons in humans too tend to conduct impulses the fastest but this is also because these axons are invested with the thickest layers of myelin. You can feel the difference in speed of conduction of various different axons which depends of the axon thickness. If you smash your toe you are almost immediately aware of it because of the initial non painful sensation felt that travels through to the brain over the thicker touch sensation axons. You may anticipate a wave or pain coming only later, because the axons carrying painful sensation are so much smaller and slower conducting axons. These groups of axons will be traveling in the same pathway. A group of axons runs in parallel making up a cable of axons which is a nerve (called a tract in the CNS).
If myelin is affected serious disease is the result. In peripheral nerves Guillian-Barre disease affects myelin and slows or blocks nerve conduction. Here one's immune system is made to attack the myelin covering of nerves. Inflammatory white blood cells invade the region surrounding axons and help to destroy myelin. Signals can't get through. A severe paralysis can result as well as numbness and other changes in sensation. Some similar problems occur in the central nervous system with a similar process resulting in inflammation and destruction of myelin in multiple sclerosis. Both Guillian Barre syndrome and multiple sclerosis are diseases of myelin.
When you consider the central importance of the shape of the neuron in its function, you begin to wonder what determines the architecture of each cell. In part, this is built into the genetic code, but think of the enormous amount of information would have to be stored genetically were genes to specify exactly the hookup of each and every cell. This would be impossible. Connectivity and shape needs to unfold and develop within the lifetime of the organism and is part of a cascade of events that unfolds in the embryo. Later, this modifies further as the effects of learning and experience are reflected in the formation of new synapses and alter the cell shape, perhaps by creating new axon and dendrite sprouts. The exact positioning and structure of supporting cells like blood vessels and glia have their own effect in determining the final structure or design of the neuron. Undoubtedly there is a constant feedback loop of interaction between neural transmission and structure that determines it. The structure determines function which determines structure in a sort of continuous dialog.
Let us take the case where the axon synapses with a dendrite (illustration) the axon of the first cell will carry an action potential that will invade the terminal. As described we would then expect a release of a chemical neurotransmitter from the axon bouton. Vesicles containing quanta of this chemical would fuse with the cell membrane and many molecules of this powerful communicating substance would be liberated into the immediate space between cells, i.e. the synapse. the transmitter will reach the membrane of one (or more) of possibly thousands of dendrites of the second or post-synaptic neuron. The transmitter is not absorbed by this membrane but instead exerts and effect on a receptor protein. this post-synaptic membrane is studded with such specially designed receptor proteins (specially designed because they fit stereoscopically pretty closely to the physical and electrochemical shape of the transmitter.
What happens next is that after fitting closely the receptor protein is altered in some way, usually so that there is a conformational change in the membrane and certain ions, for example Sodium are now allowed to traverse the membrane in small numbers. This will change ordinarily minutely, the electrical properties of the post-synaptic neuron. Alternatively the receptor protein will affect other intermediary proteins ("second messengers") within the cell to exert an effect. A direct electrical effect will be felt just very close to the actual area in which it occurs. This is why the exact structure of the postsynaptic neuron with all its dendrites is so critical. A single event at a single axodenritic synapse means next to nothing to a cell with thousands of such contacts. This signal will ordinarily be lost and have no effect. What becomes of it strongly depends on what is happening in other dendrites in the area who will also be involved with their relatively tiny bursts of transmission and ion fluxes. If enough of them get together within a short enough space of time what will happen is that this individual neuron will be made to fire with its all or none action potential. Anatomy and cell structure help determine just how these interactions occur within the matrix of space and time. Each cell comes to a decision based on precise spatial and timing characteristics, determining whether or not to fire. There are inhibitory synapses and excitatory ones so that negative and positive influences are made to summate. Add to this the effect of internal and external chemical and electrical modulators determining the state of excitation of an individual neuron.
The concentration of Calcium at an axon bouton helps determine the amount of transmitter released. If there is less Calcium, less transmitter will be released with each excitation. Certain changes can take place, with repetitive stimulation that ultimately can alter behavioral responses. An example is given in experiments of habituation in the sea hare[2] (Aplisia) that occurs on a cellular level. Habituation refers to behavioral responses that decrease with repeated stimulation. You're reading and you suddenly hear a loud noise. You have to get up to check it out. You go back to what you're doing and hear some other sounds. Perhaps then you look up. Pretty soon you are going to continue working and ignore the extraneous noise. You've habituated. This is an obviously adaptive neurological response which it has been shown can take place at the cellular level. Aplisia will contract its gills when its mantle shelf is stimulated. An axon coming from a sensory nerve excites a motoneuron controlling gill contraction. But with repeated stimulation, pretty soon the sensory axon will start to secrete less transmitter. This is attributed to an altered Calcium concentration at the sensory axon bouton. The point here is that a rather advanced behavioral phenomenon is explained on the basis of a subcellular event.
Habituation is one kind of learning, a change in neural response that happens as a direct result of exposure to a stimulus. Habituation in Aplisia thus may model how learning takes place even in more complex situations. Ultimately a change has to happen at the level of the individual cell. But even habituation which is only one kind of learning has wide variation. It happens with a disorder of the middle ear causing vertigo due to a signal mismatch between balance organs of the two ears. Eventually the brain adjusts and dizziness and vertigo diminish or habituate. Exercises that cause vertigo are routinely prescribed to decrease the response of the brain to the ears signals and thus relieve vertigo. Habituation plays a pivotal role in drug addiction. The body begins to respond less to a given dose of an addictive drug and requires more to get the same effect , increasing craving for the drug. The neural mechanisms are very different in each of these instances to habituation, which is a type of learning, and no one is saying the specific process found in the sea snail relates to these kinds of habituation.
The very same configuration of synaptic influences exciting the cell at one point may not produce an action potential at another time. There are chemicals secreted within the individual neuron that modify the cell's response, changes related to such factors as fatigue and other modulating influences coming from higher and lower levels within the nervous system. The axon secreting the transmitter is subject to influences as well. Some of them have presynaptic synapses that modify the amounts of transmitter released. There are humoral factors i.e. hormones that affect cell's level of responsiveness.
It is apparent that individual neurons can respond at much higher levels than they do in an intact healthy person. Higher nervous control occurs mostly through inhibition. As we have observed, the main effect of higher level input of the brain on the spinal cord is to decrease the deep tendon reflex. Cut off the influence of the brain or higher centers (for example by cutting the spinal cord) and you will have wildly active deep tendon responses. In patients with severe spinal cord injuries there is a host of severely active uninhibited responses. The urinary bladder may contract violently causing urgency while the sphincter muscle, also uninhibited, contracts, blocking the outflow of urine. Slight stimulation of the foot which in the usual case would cause no withdrawal at all, can cause a violent triple flexion response and even a pronounced sympathetic output, including profuse sweating, blood pressure fluctuations and even erection. Lower spinal cord mediated responses, now liberated from higher influences.
Inhibition of the same type occurs within higher centers, even the cerebral cortex. Certain degenerative diseases that cause a loss of cortical neurons produce an overreaction to stimuli. For example a sudden stimulus may cause your whole body to jump. In some diseases sudden total body jerks called myoclonus happen even with minimal stimuli. These are disinhibited cortical responses and have to be considered as part of an orientation response to new stimuli. For example, if you suddenly hear a loud sound, your whole body will jerk. This is bound to occur particularly in a quiet contemplative environment. Repeat the same stimulus and very soon, no sudden jerk will occur. Similar total body myoclonic jerks occur in the early stages of normal sleep. Under certain pathological conditions sudden jerking is seen in relation to any slight stimulus, stimulus sensitive myoclonus. The entire body will jerk with any new sound that interrupts the background.
These sudden starts have an electrical counterpart in the EEG which can show high amplitude sudden generalized electrical spikes. Evoked responses, which track the brain's electrical response to sensory stimuli often show giant electrical potentials over the cerebral cortex. We see this in conjunction with severe disease of the gray matter. An example is dialysis encephalopathy associated with the buildup of Aluminum in neurons of kidney dialysis patients. Another is with serious degenerative conditions such as Creutzfeldt-Jakob disease caused thought to be caused by a primitive virus like organism, a Prion. Certain childhood diseases cause similar but not completely identical high amplitude uncontrolled waves to occur over the cortex including subacute sclerosing panencephalitis caused by the measles virus.
These disorders have many features in common. They all involve degeneration and loss of cortical neurons and electrically we can see giant potentials over the cortex which clinically loosely correlate with myoclonus. Most importantly they indicate that so called lateral inhibition occurs right in the cerebral cortex, that higher cortical neurons simply inhibit other higher cortical neurons. The brain simply isn't revved up to respond as strongly as it possibly might. Rather, there are intrinsic mechanisms that exert control and specifically by the mechanism of inhibition.
The cerebellum is the major organ of motor control of postural and fine movements in the extremities. The output of the cerebellum seems to be entirely through large neurons, the Purkinje cells. Their influence on other motor centers seems to be entirely inhibitory. It's easy to see that control is accomplished largely via inhibition, after all, this is the major mechanism of political and military influence and why should the brain be any different? Perhaps control is accomplished universally through inhibition. Lest we become convinced that this is the case we should consider examples in which higher control occurs through the initiation of action as in the cerebral cortex which is the theoretic author an initiator of motor movements.
The cerebral cortex, as the major initiator of movements, has intrinsic mechanisms to inhibit them. This is partly, no doubt, in keeping with the cortex's role in control of movements. Also we know when electrical discharges go out of control as in an epileptic seizure, the cortical neurons have mechanisms that suppress such discharges. This mechanism may occur simply as a matter of fatigue. For example, we know that a neuron that fires, is unable to fire for a variable period which for each individual cell is its refractory period. The electrical properties built into each cell simply dictate that neurons are unable to fire at more than a given frequency. There are other mechanisms that inhibit neuronal firing. These include simple fatigue and the inability to function once certain nutrients such as oxygen and energy sources supplied by the blood are used up. The neuron's intrinsic mechanism for energy utilization that resides in its mitochondria, also plays a role.
What happens if neurons or groups of neurons continue firing as occurs in an epileptic seizure? Due to the above mechanisms neurons are unable to continue to fire and the most actively firing neurons are the ones most actively suppressed. certain patients may have a seizure that come from an uncontrolled electrical discharge in the right frontal lobe. This will cause uncontrolled repetitive movements on the left side of the body, say, depending in the group of neurons involved in the left arm. For a while the left arm will jerk repetitively. But later, the left arm will stop jerking. If we examine this person just after the jerking stops we may find that his left arm is paralyzed, that it just can't move. This is because the neurons responsible for the discharge are temporarily unable to function and it is called a Todd's paralysis. If a doctor examines a patient after a seizure and finds signs of paralysis in a specific area, he can safely assume that the seizure was initiated in the area of paralysis. The area of the brain corresponding to the paralyzed limb (in our case the right frontal lobe that initiates left arm movement) may be permanently damaged due to some other cause. It is just as possible that neurons may either be suppressed or exhausted from the previous vigorous uncontrolled firing from a seizure. It is clear that cerebral mechanisms of inhibition are at least as important as initiating mechanisms.
Just as in a Todd paralysis the most actively firing neurons are most actively suppressed there are all kinds of regulatory mechanisms, likely feedback loops that suppress a single region out of control. New PET data has shown how short lived normal transient emotions that we all experience such as sadness, differ from chronic pathologic emotional states such as clinical depression. Although you wouldn't think so somewhat different areas of the brain are involved. And it may be theorized, mechanisms that suppress active emotive areas of the brain, after an appropriate period of activity may be disordered. An active brain areas perhaps in the amygdala, a part of the limbic system, is not sufficiently suppressed and we have what amounts to an uncontrolled unmodulated "emotional seizure". Emotional disorders seem then to implicate controlling, modulating, suppressing brain mechanisms. At this point much of this is speculation but it may explain how antiepileptic agents such as Tegretol and Depakote, general inhibitors and suppressors of electrical activity, have recently been found to work quite well in affective disorders such as manic-depressive psychosis.
The general trend in neurology in the Nineteenth and earlier in the Twentieth century, emphasized pathology. Most clinicians were also versed in pathology. Pathology was the linchpin of neurology training even in my own training just twenty years ago. Then what distinguished various diseases, what always defined these disorders, was a distinct pathology in the brain or the nervous system, a lesion you could define. At that point you would know if there was anything you could do to help (usually not) and there was a satisfying feeling of recognition of the disease and your ability to predict its course. I was being trained in the era of the lesion, an abnormality to be identified either grossly or under the light microscope. The lesion defined the disease and the greatest bulk of information on how the brain works, could be inferred by seeing what happens when a part of it broke down or went out of commission.
We learned a lot by approaching our subject matter in this way. Just some of myriad examples are that the anterior periSylvian region of the left brain termed Broca's area controlled the motor aspect of making language. The posterior peri-Sylvian area in the Temporal lobe connected with language reception and understanding. Wernicke's area, the basal ganglia deep in the brain, the frontal cortex, and the cerebellum each contribute to smooth motor function in their own way, that we know about from seeing what occurs when the function of these areas is destroyed. The aim of the clinical exam was to localize the problem in the nervous system, to decide whether what the patient had, had to do with the spinal cord, or cortex or brainstem or cerebellum or some other structure. The great clinician, only just a few years ago, was the best at localizing and only after discovering the locus of the problem, would take the next step and hazard a diagnosis. We talked incessantly about localization in those days. It was with the increasing popularity of the of computer, that talk of localization got translated into the jargon of the module. The brain, when all is said and done has a distinctly modular structure. The whole nervous system, indeed the whole person, is nothing more than a series of modules, little substructures that perform their specialized routine. Ruined your knee or hip joint? Replace it. Done your heart in? Transplant it. It is not quite that simple for the nervous system or brain because it tis heavily interconnected and performs even simple task with the aid of extensive communication. This is the function of the white matter, and all of our peripheral nerves, which carry information. Today we can even watch, with the aid of technology, electrophysiolical tests such as computerized EEG or on PET scans that look at metabolic function in areas of the brain, how even the simplest sensation, ramifies or travels throughout what is really a whole integrated neural structure. As such we have started to appreciate the function of individual parts of the brain and the integrity of the whole structure simultaneously.
But to the greatest extent, analysis, the separation of the nervous system into its anatomical parts, the assignation of specialized function, is extremely useful. For the person with Parkinson disease in which you can see degeneration in the Substantial nigra, a loss of its normal blackness of pigmentation and severe dropout of neurons, you may be able to transplant cells, hopefully from a fetus whose cells are immature and may be able to grow. Or you can create yet another lesion in the group of cells that ordinarily counteract the substantia nigra's effect, with a pallidotomy which burns a hole in the globus pallidus. I mention all of this merely for purposes of illustration. Just as in a computer or a car, you strive to find out what is wrong and what needs to be replaced, or beefed up, depending on your particular problem, the hard drive, memory chip modules, and so forth, so the brain is conceived as merely a conglomerate of interchangeable modules in a "plug and play" structure.
I started deliberately with the argument of the ultimate lesion experiment, brain death. We saw that even in this extreme case there were unanswered questions. What is the organizing structure of the brain? How do we account for the sensation of consciousness, that is the feeling that we all have that we are alive? Should the brain be thought of as a conglomerate of different modules? The argument then shifted frequently from macro to microscopic. This is because each view has a great deal to contribute.
The Brain is Not Different From Other Organs; It is Peripheral to the Purpose of the Organism
From this vantage I began discussing the concept of the brain lesion. Along the way we saw for the first time how various brain regions function. When a lesion develops, the organism will continue to function as a whole, unless that lesion is lethal of course. He will find some way to survive, often by finding some inventive way to get around the impairment and, if possible to preserve the very function impaired. If a stroke destroys a large part of the left frontal cortex controlling verbal expression, the frustrated subject will still try to express himself. As we have seen this struggle to get around the effects of a brain lesion is not at all different from a person hobbling on a broken leg. In examining individual brain functions we see a common pattern and we are forced to draw an inescapable conclusion. The brain is not different from any other physical entity in the body, any of which can be diseased enough to hypofunction and cause a deficit. The organism is left in the same boat in any case, still having to find a way around that deficit. And we have come to see the brain, any of whose parts we have so far described and mapped out function as a sort of tool or instrument of one's will, somehow peripheral to a basic purpose or desire. We have not yet been privileged to find the anatomical locus of this basic driving will, nor can we be optimistic that it will ever be found anatomically within the nervous system. Moreover we have come to see by repeated example just how much neurons and the organic structure of the brain, resembles all other organs, also subject to disease, aid function while intact, but produce their own deficits in a diseased stateF.
In many patients it is possible to witness the accumulation of disease in various brain regions or anatomical modules. Many persons suffer multiple brain strokes that pick off brain volumes one by one. Some degenerative disorders like Alzheimer disease accumulate damage to multiple brain regions. And so it is possible to see, "the bright lights of the brain extinguished one by one like lampsy " , in the words of James Joyce the destruction of brain modules. But all the while, until the very end you witness simultaneously a struggle to function despite the existence to a deficit. The Alzheimer sufferer will write things down when suffering from a memory disturbance, striving to function, to limp in that broken limb. And what you discover in all of this, and this is the most profound lesson of the lesion experiment, is that that the brain like other organs, is still peripheral to a central will, still an instrument that helps us to accomplish the tasks of life, exactly like a leg, a liver or kidney, no different from any of these entities. So that therefore even after the study of the brain, there still remains some central principle, some kernel of self whose physical and anatomic boundaries are uncertain at this point. This does not diminish the fact that it is possible to build up so many modular destructions, that you will eventually see the dissolution of the whole personality, as eventually occurs in such degenerations as Alzheimer's, but again this very same phenomenon can be seen in disorders of any other organ system, any of which can spell death.
Dealing with Alzheimer's disease is difficult not just because it is, from the practical sense, for patients and families so difficult, but also philosophically. You witness the total dissolution of the personality over a relatively short timescale. In other disorders this short deterioration is even accelerated. I'm speaking about so called slow virus disease such as Creutzfeldt-Jakob disease in which we lose the sufferer in a matter of months rather than years. In Alzheimer’s what happens as the months progress is that generally there is, of course, a diminishment of abilities. Whatever was once recalled automatically requires attention and needs to be written down, otherwise it will get lost. Appointments will be missed; items will not be picked up at the supermarket. Then there will be other problems in functions that we take for granted, getting the proper change, balancing a checkbook. The speech may take on a little more halting quality and may be hesitant and unsure. At an early stage, and surprisingly for a very long time in some cases even in more skilled occupations, not requiring acquisition of a lot of new information, a doctor or lawyer even may function, without any protest from clients or co-workers for a surprisingly long time. And as a general rule, most premorbid reactions and adaptations continue to hold; an easygoing person, continues to be easygoing, a depressed or irascible individual stays that way, but in some cases, spouses particularly notice that there is a personality change. In some cases a man can feel the decline in his abilities and denies this or reacts to it, so that a once likeable character becomes a bear, always angry and defensive. At some point, he retreats from former interests and hobbies, pleasures that used to make life worthwhile and leads a constricted limited existence. Performance, one's own occupation, whose skills for the most part, had been acquired many years earlier and are relatively resistant to alterations in learning ability and recent memory deficits, now become noticeably impaired. Colleagues, co-workers, and clients now find the person's performance unacceptable and our subject is forced to leave his occupation. Later on even simpler motor and sensory, linguistic, logical functions disappear. Movements and gait and sight may even be disturbed on an inexorably descendant path of deterioration that leads to death. To some degree this may describe a sort of accelerated aging, as many capacities fail in the very old. In Alzheimer's the decline is more certain to be global, in the ultimate sense, no ability will be left untouched.
What I am trying to get at though is that in seeing this time and again, one begins to wonder whether there is an enduring permanent personality structure, after all this is what is meant by the personality, enduring attributes in a human person, or whether whatever we see that makes a person, is entirely determined by function as we see it at a given moment, of nervous structures. This question comes to the fore in seeing impaired individuals and how they cope. To some degree, a person's coping strategy remains the same as he continues to experience the throes of his illness. An easygoing optimistic person may sometimes remain optimistic and rarely becomes abusive, a bear remains a bear, but this is by no means always the case. In some cases the person changes the basic way they react to things. He seems to be a different being, a different person. We have a situation where a person makes a dramatic change in self. In the general sense, not only with Alzheimer's disease, though this is a dramatic example, persons change, are transmuted, during the process of living out their lives.
We know that persons do, change dramatically. Suppose we believe that something of the person endures after life, that there is a heaven or a hell. Then there must be some notion of an enduring object some unchanging entity that is sent to a heaven or a hell. But as we have seen the personality, at least the manifest personality, changes throughout life, sometimes slowly by development and life experience, sometimes dramatically with a serious brain disease, but the personality structure is a moving target. Which person goes to the afterlife, the child, the adult, which adult the 25 or the 50 year old defines the individual. This non-fixedness of the person makes notions of heaven and hell less tenable. After considering Alzheimer disease and the powerful effects such a disorder has on the basic personality structure it is reasonable to ask if there is, in fact, anything to a person except what may be defined by organic machinery.
As we have seen the way out of this conundrum is to concede that the brain and the body, and all that is organic or biological, is a base for what makes us human, permits us to act and to feel. To a certain extent we can live with some malfunction or hypo-function of these structures. If we have a deficit, we somehow get around the problem as long as we are able and there is no insurmountable accumulation of deficit caused by hypo-function. Biology, mechanics and bodily function serve as a platform. Take this platform away and the person disintegrates. An intact platform makes possible the performance of life work, like a diving board, or even better, a sort of launchpad. We are mistaken when we see this biological function as being all there is rather than observing that it all is necessary but not sufficient to explanation.
In the latter part of our century we saw an explosion of techniques that have allowed us to dissect the microscopic functions of the cell and its various organelles. We have witnessed breakthroughs, in biotechnology, electronics, neurochemistry , genetic mapping and cloning in particular that emphasize a complementary microscopic and sub-cellular view of neurophysiology, so that in subsequent illustration we found it beneficial to alternate from macro to micro processes, have achieved a fusion of these vantage points. We have come to see the tiny neuron as a mini-executive, a decision-maker dependent on sometimes tens of thousands of different inputs, yet through all of this examination, we have not been able to come up with a specific locus of an initiator of thought or action. Indeed the best anyone has been able to come up with is a picture of the brain as some type of grid of interactive modules that vaguely sets performs unitary actions. Yet our understanding of how biological processes affect consciousness, making that critical step from the mechanical to human experience, still eludes us.
We have seen, the attribution of all thought, perception and logic to biological processes is epistomologically speaking, unsettling, for at base, if all perceptions occur automatically, result from chemical and physiological events, then how can we do we view truth? What is real if everything we sense and believe results from automatic determined biological events? On the other hand seeing biology as a mere intermediary, an instrument of awareness, is much more palatable. An idea, even the simplest idea, the thought that we might move a single finger for example, originates in some, as yet unknown place. The act , or thought, is carried out using biological instruments and may be scientifically studied with instruments sensitive to biological events, EEG's , PET scans and the like. We ought not to be deluded into thinking, in watching these events occur in the brain, that the brain initiates thought and feeling, for that there is no evidence at all. The brain is used, just like an arm or a leg or one's eyes to accomplish life, experience and action. Study neurological events as we might, we are still at a loss to explain the origin of most action and experience. What we have done, is examine intermediary events that are expressed biologically.
In the field of neuropsychology our fund of knowledge is large and expanding. We have defined illnesses mostly, that affect human behavior, and have graduated from an erroneous position common not very long ago, that all behavior results from reflexes, action and reaction upon a nervous system which reacts automatically. The deep tendon reflex (knee jerk) is less a model for behavior, than a symbol of automatic action. Neural circuits yielding automatic behaviors are modulated by other circuits upstream, closer to cortical control centers; hard-wired neurological events are only the beginning neural function. Biological and chemical models are limited giving us at best a partial view of a whole behavior. More important, they help us to find a way to intervene should something go awry in this basic circuitry, but never provide a comprehensive explanation for behavior.
Computer models of brain function are helpful, but incomplete. The computer is like the brain in the sense that it functions as a tool or intermediary and never initiates action with a plan though with some sleight of hand it can be made to appear to act on its own accord. Computer scientists have long ago past the time when expert systems were to take the place of experts. These systems again are used somewhat successfully as tools, repositories of rigid logic and information, by some experts but have failed achieve human levels of function. Similarly navigation, locomotion, visual recognition programs have inherent flaws that are unlikely to be overcome by increasing computer power, the so-called, "brute force" approach. Rather a paradigm shift will probably be necessary, perhaps more accurate knowledge of biological function which appears to be taking on a more and more pedagogical role for computer scientists, will be useful.
What is the neurology of thought? I have talked about the permissive effect brain function, a platform or diving board mode. It the brain is working, it allows a person to function at his highest level. Biology that makes awareness possible, has mortality built into it. All living things die. Thought on the other hand, especially certain more abstract or deeper thoughts, do not die. Hannah Arendt ascribes this association to Greek Philosophy.
"Part of the Greek answer lies in the conviction of all Greek thinkers that philosophy enables mortal men to dwell in the neighborhood of immortal things and thus acquire or nourish in themselves "immortality in the fullest measure that human nature admits." For the short time that men can bear to engage in it, philosophizing transforms men into godlike creatures, "mortal gods," as Cicero says. (It is in this vein that ancient etymology repeatedly derived the key word "theorein" and even "theatron" from "theos.")"[3]
My only criticism of this concept is that Greeks didn't think of Gods the same way we do. Greek gods, it has been pointed out, were immortal but not eternal. The beginnings for Greek gods were the same as for men. They're all born at a certain instant and were not thought as being beyond time or timeless. In fact Greek gods aren't like God at all but are rather like noblemen and women, elite personages really, who by virtue of noble birth are able to live separate from the common rabble, and being idle, not having to have to earn a living as commoners do, are able to consider higher, non-practical or worldly things. Hence man, through contemplation becomes god-like, is ennobled only in the basest sense really. He can be idle like a nobleman, but is not therefore elevated to any godlike status as moderns would understand this according to the teachings of Judaism and ChristianityF . However the very notion that man is through the machinations of his intellect, escaping to some degree the mortality dictated by his biology is very attractive. It's interesting that the brain, obviously a biological organ, secretes thought, even abstractly, nobly, so that we have come full circle in our thoughts in their fullest sense. Man's peculiar biology that is the superior function of his brain is what gives him the wherewithal to escape from his biology. Mortal attributes yield immortality.
The common man is prisoner of his own biology, rarely venturing beyond the confines of a prison cell, wanting nothing but the satisfaction of his basic needs. Put another way, he ventures rarely from his bioplatform, and thus is little more than an animal. If he is hungry he will have food, which he consumes without limit. If he is aroused, sexual partners are readily available. He doesn't have to be, yet seems obsessed with the prompt satisfaction of his craving. As his trophy for his efforts, he's subject to the pathological effects of obesity, and his offspring of whom he takes no account, and women he has had, are spread over the landscape. He will never want or delay any wish or need and so remains constrained with base depravity and disease. Others are severely impaired by conditions that never allow them to consider anything except their own physical being. Some developmentally disabled or demented persons might fall into this category, but also a lot of people who are physically ill. Since curing these conditions happens rarely if at all, medical practice is mostly about helping the afflicted get beyond their limitation and condition, by lessening their symptoms, but more frequently, utilizing compassion and advice and education, providing a path to a fuller life. We ought never to complain that a condition is incurable but instead use our best formulations to find a way around it, a crutch and cast for a broken leg, a training regimen and medicine for an asthmatic Olympic swimmer. This includes cognitive techniques as well as physical ones. Persons who have stunted development due to disease are imprisoned by their physical conditions. The most rewarding part of medical practice is helping them break out. Rarely you will find a soul who though severely ill will not give up, whose inner fire cannot be extinguished and then there is shared exhilaration, symbiosis almost, between doctor and patient.
Most of us are not physically ill. We limit our own cognitive capacities to practical and physical matters anyway, turn away from a reason for being, live our lives as automatons in a purposeless existence that is sure to be extinguished when our bodies die. We know of nothing else, want nothing, strive for nothing, except acquisitions and physical comforts. Those persons who consider nothing beyond themselves are as imprisoned by their biology, as the sick patient. They are locked in the mundaneness of the real world and have never really considered anything beyond. Neuroses literally engulf them and ruin their lives. They remain oblivious to the beauty of the night sky, immune to the power in music, unvexed by any profound idea, insulated, invulnerable to anything except the mundane and insignificant. They may be happy, though their joy is superficial, their responses wooden and mechanistic. What does it matter for such persons when they come to the end of their lives? How do they differ from any other animals, a crab or an insect which has no care for anything except self-preservation? Those persons are in a prison too, so much so that your may try, without success to awaken them from their coma, rattle them, motivate them to escape.
Twentieth Century neo-modernist dictators have reveled in biology as well, at the same time being unable to escape from biology's limitations, in their interpretations and misinterpretations of it. Why should they not? They have far more technology now at their disposal. Absolute rulers from Stalin to Hitler have exploited physicality for their own ends in order to convince the world about the superiority of their regimes. They stop at nothing in competition with freer governments. Only since Glasnost have the excesses of Soviet Olympic competition been revealed. We have read stories about selection of toddlers for a servile life of athletic training, of special feedings and mistreatment used to prevent growth, the illicit use of hormones for smallness and short stature and even forced pregnancies among young gymnasts, in a misguided effort to help them absorb nutrients with forced abortion too, done before pending competitions. The pseudoscience of Nazi regime, was extensive too, ranging from transformation of Darwinism to an Ubermensche (man and superman mentality), alteration of physical anthropology to create racial superior and inferior castes, to the infamous experiments of Dr. Mengele and others. For a while there was weak debate about the ethics of using Dr. Mengele's "medical data", on the effect of heat an freezing on human subjects until someone actually reviewed it and found it, not surprisingly, to be quite useless, not up to scientific standards[4]. Of course the Nazis were not beyond the using of the Olympics as a bully pulpit for their own propaganda machine, most notably in the Munich games. We have seen how the point of view that a human is no more than a beast is a self-fulfilling prophecy. We are inured by this time to mass graves and giant bulldozers unearthing mounds of human flesh. Religion for some is the cult of the body. The physical, the savage instinct is all.
Despite the remonstrations of ne'er do well icons of scientism like Carl Sagan and others who while hoisting scientific information to new heights, and moralism and ethics that supposedly can come from an enlightened understanding of biology and of all scientific principles, and they do make a good argument for altruism, all of their thought is anemic when you consider the workings of nature, and especially as you hold them up against more demonic believers in pure biological physicality, Hitlers, Karadzichs, Noriegas and their ilk. Deepest respect for biological principles, alone while ignoring what in humans goes far beyond biology, will have cruel results. It dehumanizes man, makes the individual far less important, denies the basic non-biological self, imprisons the person and profoundly limits ethical considerations.
Our feet are firmly planted in the real physical world. We have to go about our work make our living, bring up our families, perform our functions. But a part, sometimes a relatively smaller, sometimes a larger part of us is in a different world, less physical more expansive, non-tangible, more friable, yet eternal. Our hands and our eyes point to the sky. We are some to a greater, some a lesser extent, part of some vast web of being. Without the practical and biological, we cannot enter this second higher plane, biology is necessary, it has a permissive effect. But more and more we will see humankind breaking free of biological limitations empirical evidence of an alternate existence beyond a practical and physical biology which is by all appearances, the very reason for even our physical being.
The alternative to this vision of humankind’s reaching for the sky is that we are embedded in amber biology, caught in time as some petrified insect. The consequences of this line of thought are destructive, an excuse for the bestiality we have witnessed in our Twentieth Century. I'm presenting here not a rejection of the scientific method, but a humanistic version of the pathway to the truth, a system which revels in our biological origin, if only because we can now use this information to better the lot of humankind (if not for the pure love of studying who we are and how we came to be), all the time making us aware of the greatest potential for us which is the future.
The brain is the bully pulpit of consciousness, a bioplatform not duplicated in any computer mainframe. Bioconsciousness ends with death, greatly feared by all animals, a fear reaching eloquent expression in avoidance responses and in man with desperate imaginings of eternal life. Kill an animal and you throw away a computational device more wonderful and powerful than any human contrivance. Whether it may one day be possible to reproduce by design what is accomplished in nature in the bioplatform of the brain, is a matter of conjecture. Thinking will be relegated to our own brains for the foreseeable future. The brain, aided by various assistive devices expanding its limitations, will be center of cognitive activity and executive planning for a long time to come. If we are to transfer our consciousness into a machine or reproduce it, limbic emotional, cingulate, frontal, temporal lobe, afferent sensory and motor modules among others would be necessary and even then, we have no way of knowing whether the whole may still be much more than the sum of interconnected parts.
As of this writing, no one has proved that the brain is anything other than an instrument or tool of awareness. No one has found is or is likely to find that part of our anatomy, that piece of matter authoring, initiating the simplest behavior. It’s not that we haven’t tried to find complete biological descriptors. We’ve just found biology inadequate to the task. Different methods have been employed. We have dissected conscious, subconscious, dream and even hallucinogenic states. We looked at whole and partial brain lesions, described them functionally physiologically, looked at cells and disease processes at the sub-cellular level There are still other strategies for attacking these problems, as we shall see in the next chapters. After all is said, biology is inadequate to explain all that is human. This implies that there must be a principle as yet undiscovered that is beyond biology.
Not only are biological and mechanical explanations for humanity insufficient, they are also extremely limiting. Freed of these shackles, breaking out of our biological shell or cocoon, the possibilities for our future are truly limitless. If we can simply admit that this is so, leaving aside our pride in scientific discovery and belief in mechanistic explanations for human experience for one moment, then we will find with the instrument of our human brain, such as it is, as a mere beginning.