Basic Neurochemistry and Psychopharmacology

Basic Neurochemistry and Psychopharmacology

Channel functions operate primarily with the classical neurotransmitters glutamate, aspartate and GABA. The state functions too operate with these same neurotransmitters, but also with a number of others, such as serotonin and dopamine. The latter terms may be familiar to you because psychopharmacologists work constantly with these neurotransmitters – and herein lies an interesting connection. It is no accident that the most familiar aspects of psychopharmacology deal with these chemicals, which convey the influence on the brain of the internal milieu – the “drives”. What then, are the chemicals that govern the internally directed systems?

The first is the neurotransmitter acetyicholine (Ach), which is employed by a good many neurons throughout the brain. Neurons using this neurotransmitter are called cholnergic neurons, and two such systems are of specific interest. The first cholinergic system arises in the mesopontine tegmentum (part of the reticular formation, in the back half of the pons). These neurons project via the thalamus and influence the cortex in a fairly global way.

Only the cell bodies of these acetyl-choline-producing neurons are found in the brainstem structures of the pontine tegmentum. The axons of these cells extend into sites in the hypothalamus, thalamus, and cerebral cortex, to other cells and modify the firing rates of those cells with Ach having narrow sites of origin (cell bodies clumped together in nuclei) and broad regions to which they project (via their axons) – applies to all the systems. A second (and very important) state-dependent system that employs Ach has its origin in the basal forebrain nuclei. This system, too, globally affects the firing rate of almost the entire cortex.

The next important state-dependent neurotransmitter system has its origins in the raphe nuclei of the brainstem. These neurons produce serotonin (5HT) and deliver it widely in the forebrain. Serotonin is well known for its use in antidepressant medications – the SSRIs (selective serotonin reuptake inhibitors). This phrase allows us to expand slightly our knowledge of cellular neurophysiology. A neurotransmitter is excreted via an axon into the synaptic space, where it attaches to receptors on the next neuron and thereby increases or reduces its firing rate.

Neurotransmitters define our lives. Photo by Elena.

An additional fact is that the neurotransmitter is not lost in the second cell. After a period of time, the neurotransmitter is absorbed back into the first cell, so that it can be reused. This process of retrieving the neurotransmitter back into the first cell, so that it can be reused. This process of retrieving the neurotransmitter is called “reuptake”. SSRIs are reuptake inhibitors, which implies that they slow the process of reabsorbtion or the neurotransmitter back into the first cell. This means that the excreted neurotransmitter is active in the synaptic space for a longer period of time and excites the second neuron accordingly. Any chemical that inhibits reuptake of a neurotransmitter has the effect of rendering the neurotransmitter (in this case, serotonin) more effective by making is longer-lasting.

The third class of neurotransmitter that has its origin in a core brainstem nucleus is called norepinephrine (NE: known as noradrenaline in Britain). This neurotransmitter has its source celles in the nucleus locus coeruleus of the pons. As with other state-dependent systems, the sites of action of this system are extremely diverse.

The last of the neurotransmitters to be mentioned here is produced in a transitional region between the midbrain and the diencephalon called the ventral tegmental area. The neurotransmitter produced by these cells is called dopamine (DA). Dopamine is also produced in other sites in the brainstem, the best-known of which is the substantia nigra (well known due to its role in Parkinson's disease). This nucleus is the source of the nigrostriatal DA system (which projects mainly onto the basal ganglia), but the system that originates in the ventral tegmental area is more important for our purposes. This is called the mesocortical-mesolimbic DA system, because it acts principally on limbic and cortical structures on the medial surfaces of the forebrain. Its main targets are the hypothalamus, nucleus accumbens (a basal-forebrain nucleus nestled beneath the basal ganglia), anterior cingulate gyrus, and amygdala. This system also projects to other structures, including the frontal lobes as a whole.

The neurotransmitters just described (as well as others that we have not discussed, such as histamine, which is sourced mainly in the hypothalamus) are called neuromodulators. This refers to the fact that the state-dependent neurotransmitter systems through which they operate exert global effects, via mass-action, over and above the existing activities of the specific pathways in the channel-dependent systems. They modulate these activities, in response to the current state of the organism. Thus, for example, all cognitive operations are affected – in a relatively global way – by changes in mood, vigilance, and waking state.

The Brain and the Inner World, Introduction to Basic Concepts. Mark Solms, Oliver Turnbull.

Our cognitive operations are affected by changes in mood... Photo by Elena.

Defenses against Melancholia

Defenses against Melancholia

The two patients – Mr. D and Mr. E (Kaplan-Solms & Solms, 2000, pp.187-197) – were anything but unconcerned and indifferent about their deficits: they were absolutely obsessed by them. They also displayed such symptoms – misoplegia (hatred of the paretic limb). One of these patients (Mr.D) had only a mild paresis of the left hand, and he would have been able to use it if he had tried. However, he refused to use the hand, and he actually demanded that the surgeon cut it off because he loathed it so much. Mr. D once became so enraged at his hand that he smashed it against a radiator, claiming that he was going to break it to pieces and post the bits of flesh in an envelope to the neurosurgeon who had operated on him. This conveys vividly the emotional state of such patients.

It is interesting that the same lesion site can produce such opposite emotional reactions: unawareness of a limb and denial of its deficits, versus obsessive hatred of a limb and its imperfections. This state of affairs almost demands a psychodynamic explanation. The psychoanalyst who treated these two patients came to the conclusion that their underlying psychodynamics were very similar to those of Mrs. A: they, too, attacked their internal awareness of their loss, but rather than attempt to kill themselves (like Mrs.A), they reacted by trying literally to detach the hated (damaged) image of themselves – or parts of themselves – from the rest of themselves, in order to preserve their intact selves.

No doubt, other permutations are possible (Moss and Turnball described in 1996 a 10-year-old child, with the classic right-hemisphere syndrome, who alternated between a state of denial (anognosia) and hatred (misoplegia) in relation to his left hand. During the period when he hated it, he said that he wanted to have that arm surgically removed and replaced with the left arm of his mother).

What all of these cases have in common is a failure of the process of mourning. Underlying the range of clinical presentations was this commun dynamic mechanism : these patients could not tolerate the difficult feelings associated with coming to terms with loss. The superficial differences between the patients are attributable to to fact that they defended themselves against this intolerable situation in various ways.

Psychoanalytic hypotheses are no less prone to error than cognitive ones. Photo by Elena.

The reason mourning fails in these patients

We are in position to integrate these findings.   The right perisylvian convexity is specialized for spatial cognition. Damage to this area therefore undermines the patients' ability to represent the relationship between self and objects accurately. This in turn undermines object relationships in the psychoanalytic sense: object love (based on a realistic conception of the separateness between self and object) collapses, and the patients' object relationships regress to the level of narcissism. This results in narcissistic defenses against object loss, rendering these patients incapable of normal mourning. They deny their loss and all the feelings (and even external perceptions) associated with it, using a variety of defenses to shore up their denial whenever the intolerable reality threatens to break through.

Left-hemisphere patients, by contrast, retain the capacity for object love, for the reason that the requisite “spatial” concepts remain intact. Accordingly, these patients, whose objective loss is at least equivalent to that of right-hemisphere patients, are able to negotiate the difficult process of mourning. The “depression” and so-called catastrophic reactions of left-hemisphere patients are, in fact, healthy and appropriate responses to devastating loss. Right-hemisphere patients, however, stuck in their narcissism, cannot test their fantastic misconceptions against the perceived reality (as Mrs. K did), and they cannot undertake the normal work of mourning that Mr. J didn.

Psychoanalytic investigation of the inner life of neurological patients clearly has much to offer us. In this instance, it was able to throw important light on a syndrome that was inadequately accounted for by a variety of neurocognitive theories, each of which failed to accommodate the psychological complexities of human emotional life.

Psychoanalytic theories therefore need to be subjected to the same rigorous empirical tests. Photo by Elena.

Life in the Cosmos

Life in the Cosmos

There must be many different environments suitable for life in a given planetary system. Once life originates, it tends to be very adaptable and tenacious.

In the Solar system there are several bodies that may be suitable for life of some art: the Earth certainly (if we all live in a real world and not in a computer simulation), and perhaps Mars, Titan and Jupiter.

There is evidence that planets are a frequent accompaniment of star formation. We can see this evidence in the satellite systems of Jupiter, Saturn and Uranus, which are like miniature solar systems. Theories of the origin of the planets are based on this premise and studies of double stars confirm it. We can also observe accretion disks around stars and find the evidence in some preliminary investigations of gravitational perturbations of nearby stars.

Thus many, perhaps even most stars in our universe must have planets.

But what about life? All experiments show that under the most common cosmic conditions the molecular basis of life is readily made, the building blocks of molecules able to make copies of themselves.

We step now on less certain ground: there may be impediments in the evolution of the genetic code, although we think this unlikely over billions of years of primeval chemistry.

On the one hand, many individually unlikely steps had to occur in biological evolution and human history for our present intelligence and technology to develop. There must be many quite different pathways to an advanced civilization of specified capabilities.

On the Earth we must consider the apparent difficulty in the evolution of large organisms represented by the Cambrian explosion. Thus let us suggest that only one percent of planets on which life arises eventually produce a technical civilization.

The conclusion in interesting enough: the total number of planets in the Milky Way only on which life has arisen at least once may be a hundred billion inhabited worlds. And we repeat that we speak about the Milky Way only. That in itself is a remarkable conclusion. But we are not yet finished. One percent of plants where a technical civilization has developed, give us the total number of one billion “civilized” worlds.

Obviously, this estimate represents some middle ground among the varying scientific opinions.  Some think that the equivalent of the step from the emergence of trilobites to the domestication of fire goes like a shot in all planetary systems. Some other think that even given ten of fifteen billion years, the evolution of even ten technical civilizations in the Milky Way Galaxy is unlikely.

Anyway, this is not a subject on which we can do much experimentation as long as our investigations are limited to a single planet. Our estimation about a billion planets on which technical civilizations have arisen at least once is rather speculative. It is very different from saying that there are a billion planets on which technical civilizations now exist. For this, we must know much more about Cosmos.

How many technical civilizations exist in the Universe? We know for sure about only one by now. Image : Megan Jorgensen.

Erosion on the Earth

Erosion on the Earth

Because of erosion on the Earth, our monuments and artifacts will not, in the natural course of things, survive to the distant future. But the spaceships Voyager launched in the XX Century carry human records on their way out of the Solar system.

Indeed, brains and genes and books encode information differently and persist through time at different rates. But the persistence of the memory of the human species will be far longer in the impressed metal grooves on the Voyager interstellar record. It happens because the erosion in interstellar space – chiefly impacting dust grains and cosmic rays – is so slow that the information on these recordings will last a billion years.

But the Voyager message is traveling with agonizing slowness. The fastest object ever launched by the human species, this probe will still take tens of thousands of years to go the distance to the nearest star.

Any television program will traverse in hours the distance that Voyager has covered in years. A television transmission that has just finished being aired will, in only a few hours, overtake the Voyager spacecraft in the region of Saturn and beyond and speed outward to the stars. If it is headed that way, the signal will reach Alpha Centauri in a little more than four years. If, some decades or centuries hence, anyone out there in space hears our television broadcasts, I hope they will think well of us, a product of fifteen billion years of cosmic evolution, the local transmogrification of matter into consciousness.

Our intelligence is providing us with awesome powers, but it is not yet clear yet if we have the wisdom to avoid our own self-destruction.

However, many of us are trying very hard. We hope that very soon in the perspective of our cosmic time we will have unified our planet peacefully into an organisation cherishing the life of every living creature on it and will be ready to take that next great step, to become part of a galactic society of communicating civilizations.

Will we ever become part of a galactic society? Image : © Megan Jorgensen.

Illegal Radio Transmissions

Illegal Radio Transmissions

or Million Years Old Society

A technical civilization one million years-old has descended on the planet Earth… Would we even recognize its presence?

More important question yet: Would a society a million years in advance of us be interested in colonization or interstellar spaceflight?

In fact, it may be people have a finite lifespan for a reason. Could it be that we are so interested in spaceflight because it is a way of perpetuating ourselves beyond our own lifetimes? Of course, progress in the biological and medical sciences might uncover that reason and lead to suitable remedies.

But might a civilization composed of essentially immortal beings consider interstellar exploration fundamentally childish? It may be that we have not been visited because the stars are strewn abundantly in the expanse of space, so that before a nearby civilization arrives, it has altered its exploratory motivations or evolved into forms indetectable to us.

It would be very easy for extraterrestrials to make and unambiguously artificial interstellar message (provided that they have the same logic we have and the same mathematics, which is reasonable enough if they try to make a contact with their neighbours). For example, they could first prime numbers – numbers divisible only by themselves and by one – are 1, 2, 3, 5, 7, 11, 19.

It is extremely unlikely that any natural physical process could transmit radio messages containing prime numbers only. If we received such a message we would deduce a civilization out there that was at least fond of prime numbers. But the most likely case is that interstellar communication will be a kind of palimpsest, like the palimpsests of ancient writers short of papyrus or stone who superimposed their messages on top of pre-existing messages.

Because we will share scientific and mathematical insights with any other civilization, understanding the interstellar message coming from a very advanced cosmic community will be the easiest part of the problem. Convincing the governments to fund a search for extraterrestrial intelligence is the hard part.

In fact, it may be that civilizations can be divided into two great categories: one in which the scientists are unable to convince non-scientists no authorize a search for extraplanetary intelligence, in which energies are directed exclusively inward, in which conventional perceptions remain unchallenged and society falters and retreats from the stars; and another category in which the grand vision of contact with other civilizations is shared widely, and a major search us undertaken.

This is one of the few human endeavors where even a failure is a success. If we were to carry out a rigorous search for extraterrestrial radio signals encompassing millions of stars and heard nothing, we would conclude that galactic civilizations were at best rare, a calibration of our place in the universe. It would speak eloquently of how rare are the living things of our planet, and would underscore, as nothing else in human history has, the individual worth of every human being.  If we were to succeed, the history of our species and our planet would be change forever.

Perhaps at an adjacent frequency or a faster timing, there would be another message, which would turn out to be a primer, an introduction to the language of interstellar discourse. The primer would be repeated again and again because the transmitting civilization would have no way to know when we tuned in on the message. And then, deeper in the palimpsest, underneath the announcement signal and the primer, would be the real message. Radio technology permits that message to be inconceivably rich. Perhaps when we tuned in, we would find ourselves in the midst of Volume 6,511 of the Encyclopaedia Galactica.

Any messages transmitted from outer space are the responsibility of the BBC and the Post office. It is their responsibility to track down illegal broadcasts (pronouncement from a British Defense Department, the London Observer, February 26, 1978). Image : Megan Jorgensen.