#59. Neuromodulators as Peril Specialists [neuroscience, evolution]

NE   EV

Red: theory; black, fact

Solanum dulcamara, a plant with anticholinesterase activity.

“Life is difficulty.” -The Buddha Gautama

My PhD thesis was about a neuromodulator (acetylcholine) acting on mammalian brain. It was tough to decapitate so many rats; I never got used to it.

The basic theory

I conjecture that the primordial function of any type of transmitter substance acting on the g-protein-coupled cell-surface receptors or nuclear receptors of neurons was to coordinate the whole-organism response to some class of perils.

Table 1.

Peril	Substance	Failure mode
Extremes of heat and cold	glutamate and GABA	?
Predator	serotonin	depression
Parasite	histamine	phobia
Rival conspecific	noradrenaline	paranoia
Social isolation

#39. The 1950 Ramp [population, evolutionary psychology, engineering, neuroscience]

PO   EN   EP   NE

Red, theory; black, fact

A schematic of a simple rate-of-increase controller mechanism

Historical 

Since about 1950, the world population has been increasing along a remarkably steady ramp function with no slackening in the rate of increase yet apparent, although one cycle of oscillation in the slope occurred during the Sixties. Malthusian reasoning predicts an exponential increase, which this is not. Several lines of evidence point to the idea that humans have a subconscious population controller in their heads, and yet such a controller would have leveled out the increase by now. Until now, no theory has sufficed to explain the facts.

Human Population is Being Controlled for Endless Trouble

The natural population curve for humans in good times may be a saw-tooth waveform, with population ramps alternating with political convulsions that result in a large group being expelled permanently, resulting in the precipitous but limited drop in local population density that ends the saw-tooth cycle. This cycle accomplishes the ecological dispersal function. The population must ramp up for a time to sustainably create the numbers needed for the expulsions. The WHO population curve shows only a ramp because it is a worldwide figure and therefore population losses in expelling regions are balanced by population increases in welcoming regions. This also implies that human population has been increasing in a way unrestrained by food or resource availability or any other external constraint since 1950, to now.

Clearly, human population is being controlled; not to a constant absolute density, but to a constant rate of increase. Population density would go up along the much faster, steeper, and more disastrous exponential curve of Malthus if there were actually no controller.

Neuroscience Aspects

Researchers should look first for such a controller in the hypothalamus, already known to control other variables, such as temperature, by feedback principles.

"Nature does not reinvent the wheel" [quote from my old Professor], which I understand to mean that once a brain structure evolves to serve a particular computational function, it will be tapped for all future needs for such a calculation. This process may make it grow larger or develop sub-nuclei, but additional, independent nuclei for the same computation will never evolve.

Engineering Aspects 

The population controller may contain a conventional PID controller. To make it control rate of increase rather than absolute population density, you put a differentiator in the feedback pathway. If you are of the opinion that human population control is urgent, then you must knock out this differentiator and replace it with a simple feed-through connection. 

Back to Neuroscience 

Fortunately, one common way for evolution to implement differentiation in mammals is to begin with such a feed-through connection and supplement it with an inhibitory, slow, parallel feed-forward connection. If this is the case here, then you  inhibit the feed-forward pathway pharmacologically with sufficient specificity and the job is done. Subjectively, the effect of such a drug would be to take away people's ability to get used to higher population density in deciding how many children to have. An increased propensity to riot should not occur.

The political convulsions that produce dispersal would be triggered by the value on the integrator of the PID controller rising above a threshold. The amygdala of the brain may mediate this. Consistent with this, bilateral removal of the amygdala and hippocampus in monkeys is known to have a profound taming effect accompanied by hypersexuality, known as the Kluver-Bucy syndrome.

#33. Emotions [evolutionary psychology, genetics, neuroscience]

EP   NE   GE

Red, theory; black, fact

A Genetics Theory 

All sexually reproducing species may have a long-range guidance system that that could be called proxy natural selection, or preferably, post-zygotic gamete selection (PGS). This is basically a fast form of evolution in which particular body cells, the gametes, are the units of selection, not individuals. Selection is conjectured to happen post-zygotically (i.e., sometime after the beginning of development, or even in adulthood) but is retroactive to the egg and sperm that came together to create the individual. 

Each gamete is potentially unique because of the crossing-over genetic rearrangements that happen during its maturation. This theory explains the biological purpose of this further layer of uniqueness beyond that due to the sexual mixing of chromosomes, which would otherwise appear to be redundant.

Emotions Represent Fitness 

Our emotions are conjectured to be programmed by species-replacement group selection and to serve as proxies for increases and decreases in the fitness of our entire species.

The Corresponding Mechanistic Theory 

A further correlate of an emotion beyond the cognitive and autonomic-nervous-system components would be the neurohumoral component, expressed as chemical releasing and inhibiting factors that enter the general circulation via the portal vessels of the hypothalamus, blood vessels which are conventionally described as affecting only the anterior pituitary gland. These factors may reach the stem-like cells that mature into egg and sperm, where they set reversible epigenetic controls on the level of crossing-over that will occur during differentiation. 

Large amounts of crossing-over are viewed as retroactively penalizing the gametes leading to the individual by obfuscating or overwriting with noise specifically the genetic uniqueness of said original gametes. In contrast, low levels of further crossing-over reward the original gametes with high penetrance into the next generation. 

Here we have all the essential ingredients of classical natural selection, and all the potential, in a process that solves problems on an historical timescale.

The Limited Scope of Crossing-over

Crossing-over happens only between homologous chromosomes, which are the paternal and maternal copies of the same chromosome. Human cells have 46 chromosomes because they have 23 pairs of homologous chromosomes. 

The homologous-chromosome-specificity of crossing-over suggests that the grand optimization problem that is human evolution has been broken down into 23 smaller sub-problems for the needs of the PGS process, each of which can be solved independently, without interactions with any of the other 22, and which involves a 23-fold reduction in the number of variables that must be simultaneously optimized. 

In computing, this problem-fragmentation strategy greatly increases the speed of optimization. I conjecture that it is one of the features that makes PGS faster than classical natural selection.

Do Chromosome-specific Signaling Pathways Exist?

However, we now need 23 independent neurohumoral factors descending in the bloodstream from brain to testis or (fetal) ovary, each capable of setting the crossing-over propensity of one specific pair of homologous chromosomes. Each one will require its own specific receptor on the surface of the target oogonia or spermatogonia. In the literature, I already find a strange diversity of cell-surface receptors on the spermatogonia. I predict that the number of such receptors known to science will increase to at least 23. None of this is Lamarkism, because nervous-system control would be over the standard deviation of traits, not their averages.

Naively, this theory also appears to require 23 second messengers to transfer the signals from cell surface to nucleus, which sounds excessive. Perhaps the second messengers form a combinatorial code, which would reduce the number required by humans to log₂ (23) = 4.52, or 5 in round numbers. This is much better. Five second-messenger systems are known, these being based on: cyclic AMP, inositol triphosphate, cyclic GMP, arachidonic acid, and small GTPases (e.g., ras). The AND-element that would be required for decoding could be implemented straightforwardly as a linear sequence of transcription-factor binding sites along the DNA strand. However, many mammalian species have many more than the 32 chromosome pairs needed to saturate a 5-bit address space. If we expand the above list of second messengers with the addition of the calcium/calmodulin complex, the address space expands to 64 pairs of homologous chromosomes, for a total ploidy of 128. This seems sufficient to accommodate all the mammals. Thus, a combinatorial second-messenger code representable as a five- or six-bit binary integer in most organisms would control the deposition of the epigenetic marks controlling crossing-over propensity.

It Gets Bigger

If the above code works for transcription as well as epigenetic modification, then applying whatever stimuli it takes to produce a definite combinatorial second-messenger state inside the cell will activate one specific chromosome for transcription, so that the progeny of the affected cell will develop into whatever that chromosome specifies, be it an organ, a system, or something else. And there you may have the long-sought key to programming stem cells. You're welcome.

The requirement that the evolution of each chromosome contribute independently to the total increase in fitness suggests that a chromosome specifies a system, like the nervous system or the digestive system. We seem to have only 11 systems, not 23, but more may be defined in the future.

Illustration credit: By Edmund Beecher Wilson - Figure 2 of: Wilson, Edmund B. (1900) The cell in Development and Inheritance (2nd ed.), Category:New York: The Macmillan Company, Public Domain, https://commons.wikimedia.org/w/index.php?curid=3155599

#27. The Origin of Consciousness [neuroscience]

NE

Red, theory; black, fact

We begin life conscious only of our own emotions. Then the process of classical conditioning, first studied in animals, brings more and more of our environment into the circle of our consciousness, causing the contents of consciousness to become enriched in spatial and temporal detail. Thus, you are now able to be conscious of these words of mine on the screen. However, each stroke of each letter of each word of mine that now reaches your consciousness does so because, subjectively, it is "made of" pure emotion, and that emotion is yours.

Some analogies come to mind. Emotion as the molten tin that the typesetter pours into the mold, the casting process being classical conditioning and the copy the environmental data reported by our sense organs. Emotion as the area on one side of a fractal line and sensory data the area on the other side. Emotion as an intricately ramifying tree-like structure by which sensory details can send excitation down to the hypothalamus at the root and thus enter consciousness.

The status of "in consciousness" can in principle affect the cerebral cortex via the projections to cortex from the histaminergic tuberomamillary nucleus of the hypothalamus. Histamine is known to have an alerting effect on cortex, but to call it "alerting" may be to grossly undersell its significance. It may carry a consolidation signal  for declarative, episodic, and flash memory. Not for a second do I suppose all of that to be packed into the hippocampus, rather than being located in the only logical place for it: the vast expanse of the human cerebral cortex.

#26. Why Organized Religion? Theory Two [evolutionary psychology]

EP

Red, theory; black, fact

Emotions are an "endophenotype," a term from functional magnetic resonance imaging, that provides a useful stepping stone from evolutionary arguments to explanations of our daily lives. 

Starting with the Emotion 

What is the mood or feel as you enter a place of worship and participate in the ceremonies conducted there? More than anything else, the mood is one of great reverence, as though one is in the presence of the world's most powerful king. Kings are supposed to "represent their race." 

Problem

If the emotional outline of people's behaviour is being partly randomized in each generation by recombination-type mutations, a consistent moral code seems impossible if we assume that morality comes mostly from peoples' inborn patterns of emotional reactivity, that is, the sum total of everyone's preferences. The purpose of a king may be to find and coincide with societies' moral center of gravity, around which a formal, if temporary, moral code can be constructed. In a complex society, everyone must be "on the same page" for efficient interaction. 

It Gets Bigger

The same problem no doubt recurs each time organisms come together to form a colony, or super-organism: the conflict between the need of a colony for coordination of colonists and the need of evolution for random variability. Such variability will inevitably affect the formulation and interpretation of the coordinating messages that the colonists exchange, like all their other inborn characteristics. 

A Social Solution 

With kingship comes the corrupting influence of personal power and  tyrannical government. Replacing a real king with a pretend-king named "God" would seem to be the solution that accounts for organized religion, but then one loses the flexibility that goes with having a flesh-and-blood king who can change his predecessor's laws based on current popular sentiment.

Mechanistic Interpretation 

However, human nature may well have a core-and-shell structure, with an "unchanging" core surrounded by a slowly changing shell. The former would be the species-specific objective function and produced by species-replacement group selection within the genus, and the latter would be due to selection of smaller units, and would represent the stratagems hit upon by our ancestors to meet the demands of the objective function in our time and place. This shell part may account for cultural differences between countries. The core may be implemented in the hypothalamus of the brain, whereas the shell may be implemented in the limbic system. The core, being very slow to change, could be managed by organized religion, whereas the shell could be codified by the more flexible institution of government. Though the core is unchanging overall, specific individuals will harbor variations in it due to point mutations, necessitating the standardizing role of religion. Synaptic plasticity would then be used to cancel the point-mutational variation in the objective function.

The Big Picture 

The core may consist of four pillars, or regulatory themes: regulation of genetic diversity, memetic diversity, altruism, and dispersal. Our energetic investment in obtaining each item is to be optimized.

#24. Proxy Natural Selection from the Inside [evolutionary psychology, genetics]

EP   GE

Red, theory; black, fact

Morning hymn at Sebastian Bachs' By Toby Edward Rosenthal

What Does Darwinian Fitness Feel Like?

My first post on post-zygotic gamete selection (PGS) left open some questions, such as what it should feel like, if anything, when one is fulfilling the species objective function and being deemed "proxy-fit" by one's own hypothalamus.

How Our Emotions Program Us

I conclude that it's just what you would think: you feel joy and/or serenity. Joy is one of Ekman's six basic universal human emotions, the others being fear, anger, disgust, sadness, and surprise. I think that emotions collectively are the operations of the highest-level human behavioral program. (That is, the program in its broadest outlines.) The unpleasant emotions force you to get off the couch until they are taken care of, and joy lets you get back on. Thus, the unpleasant four are the starting emotions, and joy is the stopping emotion. 

Surprise may be a meta-emotion that tells you that your threshold for experiencing one of the other emotions is too high, and immediately lowers it. Each activation of an emotion may tend to lower the threshold for activating it next time, which implies a positive feedback loop capable of changing the personality to suit suddenly changed circumstances, especially if the emotion eventually begins issuing with no trigger at all.

Where Our Emotions Come From

To relate this to the mechanism of PGS, the crossing-over events that went into making the sperm cell that made a given person would theoretically affect brain development more than anything else, specifically connecting some random stimulus to one of the unpleasant primary emotions. This creates temperament, and thus  personality, which is the unique quality which they have to offer the world, and on which they are being tested by history. If the actions to which their own, special preferences propel them are what the species objective function is looking for, they succeed, feel joy and serenity, and experience an altered methylation status of the DNA in the spermatogonia if male, which suppresses further crossing over in the manufacture of sperm, so that their personality type breeds true, which is what the population needs. Famous musical families, for example, may originate in this way.

PGS is quick evolution to respond to challenges that come and go on less than a multi-thousand generation timescale, and it explains the complexities of sexual reproduction.

A Flaw in the Argument, Addressed

However, trees have no behavior, much less personalities, and yet they have sexual reproduction. However, trees probably adapt quickly not by behavioral change, but by changes in their chemistry. The chemistry in question would be the synthesis of pesticidal mixtures located in the central vacuole of each plant cell. In terms of such mixtures, each tree should be slightly unique, an easily testable prediction.

The Big Picture 

Each of the four unpleasant "starting" emotions may sub-serve one of the four pillars of the species objective function. Thus: sadness, altruism; disgust, genetic diversity (due to point mutations; what is motivated here is the screening of such novelties during mate selection, screening always being the expensive part); fear, memetic diversity (or motivating prescreening of memetic novelties through fear of public speaking); anger, dispersal.

Each of these emotions seems to have another use, in preserving the life of the individual, as opposed to the entire species. Thus: sadness, unfavorable energy balance; disgust, steering one away from concentrations of harmful bacteria; fear, avoidance of injury and death; anger, driving away competitors for food and mates.

Picture credits: https://commons.wikimedia.org/wiki/Commons:Copyright_tags/Country-specific_tags#United_States_of_America

#22. Proxy Natural Selection: The God-shaped Gap at the Heart of Biology [genetics, evolution]

EV   GE

Red, theory; black, fact

The Problem and My Solution 

Some entity must be responsible for compensating for the fact that our microbial, insect, and rodent competitors evolve much faster than we do because of their shorter generation times. In these pages, I have been variously calling this entity the intermind, the collective unconscious, the mover of the zeitgeist, and the real, investigable system that the word "God" points to. I here recant my former belief that epigenetic marks are likely to be the basis of an information storage system sufficient to support an independent evolution-like process. I will assume that the new system, "post-zygotic gamete selection" (PGS) is DNA-based.

Background 

First, a refresher on how standard natural selection works. DNA undergoes various mutations that add diversity to the genome. The developmental process translates the various genotypes into a somewhat diverse set of phenotypes. Existential selection then ensues from the interaction of these phenotypes with the environment, made chronically stringent by population pressure. Differential reproduction of phenotypes then occurs, leading to changes in gene frequencies in the population gene pool. Such changes are the essence of evolution.

My Solution, Big Picture 

PGS assumes that the genome contains special if-then rules, perhaps implemented as cis-control-element/structural gene partnerships, that collectively simulate the presence of an objective function that dictates the desiderata of survival and replaces or stands in for existential selection. A given objective function is species-specific but has a generic resemblance across the species of a genus. The genus-averaged objective function evolves by species-replacement group selection, and can thus theoretically produce altruism between individuals. The if-then rules instruct the wiring of the hypothalamus during development, which thereby comes to dictate the organism's likes and dislikes in a way leading to species survival as well as (usually) individual survival. Routinely, however, some specific individuals end up sacrificed for the benefit of the species.

The PGS Mechanism 

Crossing-over mutations during meiosis to produce sperm increase the diversity of the recombinotypes making up the sperm population. During subsequent fertilization and brain development, each recombinotype instructs a particular behavioral temperament, or idiosyncratotype. Temperament is assumed to be a set of if-then rules connecting certain experiences with the triggering of specific emotions. An emotion is a high-level, but in some ways stereotyped, motor command, the details of which are to be fleshed out during conscious planning before anything emerges as overt behavior. Each idiosyncratotype interacts with the environment and the result is proxy-evaluated by the hypothalamus to produce a proxy-fitness (p-fitness) measurement. The measurement is translated into blood-borne factors that travel from the brain to the gonads where they activate cell-surface receptors on the spermatogonia. Good p-fitness results in the recombination hot spots of the spermatogonia being stabilized, whereas poor p-fitness results in their further destabilization. 

Thus, good p-fitness leads to good penetrance of the paternal recombinotype into viable sperm, whereas poor p-fitness leads to poor penetrance because of many further crossing-over events. Changes in hotspot activity could possibly be due to changes in cytosine methylation status. The result is within-lifetime changes in idiosyncratotype frequencies in the population, leading to changes in the gross behavior of the population in a way that favors species survival in the face of environmental fluctuations on an oligo-generational timescale. On such a timescale, neither standard natural selection nor synapse-based learning systems are serviceable.

Female PGS Is Different 

However, egg cells mature in utero and therefore face a selection disconnect or delay. The female version of crossing over may set up a slow, random process of recombination that works in the background to gradually erase any improbable statistical distribution of recombinotypes that is not being actively maintained by PGS.

A Better Theory of Female PGS 

First, a definition. PGS focus: a function that is the target of most PGS. Thus, in trees, the PGS focus might be bio-elaboration of natural pesticides. In human males, the PGS focus might be brain development and the broad outlines of emotional reactivity, and thus behaviour. In human females, the PGS focus might be the digestive process. The effectiveness of the latter could be evaluated while the female fetus is still in the womb, when the eggs are developing. The proxy fitness measure would be how well nourished the fetus is, which requires no sensory experience. This explains the developmental timing difference between oogenesis and spermatogenesis. Digestion would be fine tuned by the females for whatever types of food happen to be available in a given time and place.

Experimental evidence for the proposed recombination mechanism of PGS has been available since 2011, as follows:

Stress-induced recombination and the mechanism of evolvability

by Weihao Zhong; Nicholas K. Priest

Behavioral Ecology and Sociobiology, 03/2011, Volume 65, Issue 3

Abstract:

“The concept of evolvability is controversial. To some, it is simply a measure of the standing genetic variation in a population and can be captured by the narrow-sense heritability (h2). To others, evolvability refers to the capacity to generate heritable phenotypic variation. Many scientists, including Darwin, have argued that environmental variation can generate heritable phenotypic variation. However, their theories have been difficult to test.

 Recent theory on the evolution of sex and recombination provides a much simpler framework for evaluating evolvability. It shows that modifiers of recombination can increase in prevalence whenever low fitness individuals produce proportionately more recombinant offspring. Because recombination can generate heritable variation, stress-induced recombination might be a plausible mechanism of evolvability if populations exhibit a negative relationship between fitness and recombination. Here we use the fruit fly, Drosophila melanogaster, to test for this relationship.

We exposed females to mating stress, heat shock or cold shock and measured the temporary changes that occurred in reproductive output and the rate of chromosomal recombination. We found that each stress treatment increased the rate of recombination and that heat shock, but not mating stress or cold shock, generated a negative relationship between reproductive output and recombination rate. The negative relationship was absent in the low-stress controls, which suggests that fitness and recombination may only be associated under stressful conditions. Taken together, these findings suggest that stress-induced recombination might be a mechanism of evolvability.”

However, my theory also has a macro aspect, namely that the definition of what constitutes "stress," in terms of neuron interconnections or chemical signalling pathways, itself  evolves, by species-replacement group selection.

#21. The Cogs of Armageddon [evolutionary psychology]

EP

Red, theory; black, fact

The Mechanism of Human Dispersal 

How does everyday human behaviour eventually accomplish the biological function of dispersal for the human race? 

Background 

Dispersal is things like dandelions shedding airborne seeds, slime molds developing into spore cases on stalks and releasing the spores into the wind, territorial systems of birds and mammals forcing the unlanded young to seek widely for their own territories, and humans going into space because our science fiction writers keep scaring us about the possibility of meteor crashes wiping out life on Earth. 

The slime mold Dictyostelium is triggered into its dispersal program by the food supply running short; I will adopt the assumption that the human dispersal program is also triggered by the end of the good times, that is, the price of bread rising relative to wages.

The Psychology of Dispersal

Human neural pathways may potentiate aggression when the hard times come, but of an elaborate kind featuring many evolved adaptations that ensure efficient dispersal (i.e., with minimal loss of life). 

Our evolved dispersal program begins with a two-person feud of the sort illustrated in cultural references too numerous to mention. An arbitrary stimulus, made offensive by some piece of Pavlovian conditioning, is traded back and forth with rapidly increasing energy. 

Features of Human Dispersal Explained by Evolution 

1) The emotional component is strongly threatening because the participants must be induced to seek allies, which people do when  threatened, until all of society is eventually polarized. The acts of provocation being traded back and forth become progressively more outrageous, as they must, to keep the polarization process going. Eventually, one side gets the upper hand and forces the other to flee.

2) The result is a diaspora, i.e., dispersal. Because of the long polarization process, an entire group is expelled, not single individuals one at a time. Thus, members of such a group can assist each other to survive and relocate, thereby reducing the mortality associated with dispersal, thereby making the dispersal event more efficient in terms of number of people relocated.

3) The group who flees is then seen by the international community as the blameless victim, and the group who stays is seen as the unprincipled aggressor. This tends to elicit a sheltering of the refugees and an intimidation of the "aggressor," who is deterred from pressing his advantage, that is, pursuing the refugees and slaughtering them to the last man, which is what each side would like to do to the other by this point. This, again, is an efficiency from the point of view of producing dispersal.

4) However, if each side is continually threatening the other, why don't they flee each other's presence during the very early stages? Humans may have a reflex that converts feeling threatened into a wish to injure the threatening party, possibly a behavioural leftover from some earlier adaptation, such as an anti-predation defence. To injure, you have to stick around. 

5) Finally, settled refugees usually do not integrate completely into the host society, instead forming ethnic neighbourhoods. Being seen as ethnic by the host society, due to slow integration, could improve the reproductive success of refugees because of disassortative mate-choice effects evolved to favor genes that produce dispersal.

6) The dispersal-producing dynamic just outlined is powerful, because it must overcome all the reasons a person would not leave their homeland forever at some arbitrary time: expense, risk of mortality in transit, opportunity costs, temporary loss of livelihood, need to learn a new language and customs, vulnerability to exploitation in the new country, etc.

#12. The Neural Code, Part I: the Hippocampus [neuroscience, engineering]

EN   NE

Red, theory; black, fact

Santiago Ramón y Cajal (1911) [1909] Histologie du Système nerveux de l'Homme et des Vertébrés, Paris: A. Maloine. The French copyright expired in 2004.

"Context information" is often invoked in neuroscience theory as an address for storing more specific data in memory, such as whatever climbing fibers carry into the cerebellar cortex (Marr theory), but what exactly is context, as a practical matter?

Requirements for a Learning Context Signal

First, it must change on a much longer timescale than whatever it addresses. Second, it must be accessible to a moving organism that follows habitual, repetitive pathways in patrolling its territory.

The Fourier Transform as Context Signal

Consideration of the mainstream theory that the hippocampus (see illustration) prepares a cognitive map of the organism's spatial environment suggests that context is a set of landmarks. It seems that a landmark will be any stimulus that appears repetitively. Since only rhythmically repeating functions have a classical discrete-frequency Fourier transform, the attempt to calculate such a transform could be considered a filter for extracting rhythmic signals from the sensory input. 

From Repeating to Rhythmic 

However, this is not enough for a landmark extractor because landmark signals are only repetitive, not rhythmic. Let us suppose, however, that variations in the intervals between arrivals at a given landmark are due entirely to programmed, adaptive variations in the overall tempo of the organism's behavior. A tempo increase will upscale all incoming frequencies by the same factor, and a tempo decrease will downscale them all by the same factor. Since these variations originate within the organism, the organism could send a "tempo efference copy" to the neuronal device that calculates the discrete Fourier transform, to slide the frequency axis left or right to compensate for tempo variations. 

Thus, the same landmark will always transform to the same set of activated spots in the frequency-amplitude-phase volume. 

A Possible Neuronal Mechanism

I conjecture that the hippocampus calculates a discrete-frequency Fourier transform of all incoming sensory data, with lowest frequency represented ventrally and highest dorsally, and a with a linear temporal spectrum represented between. 

Tempo Compensation 

The negative feedback device that compensates tempo variations would be the loop through medial septum. The septum is the central hub of the network in which the EEG theta rhythm can be detected. This rhythm may be a central clock of unvarying frequency that serves as a reference for measuring tempo variations, possibly by a beat-frequency principle. 

Fourier Transform by Re-entrant Calculation 

The hippocampus could calculate the Fourier transform by exploiting the mathematical fact that a sinusoidal function differentiated four times in succession gives exactly the starting function, if its amplitude and frequency are both numerically equal to one. This could be done by the five-synapse loop from dentate gyrus (DG) to hippocampal CA3 to hippocampal CA1 to subiculum (sub) to entorhinal cortex (EC), and back to dentate gyrus. The dentate gyrus looks anatomically unlike the others and may be the input site where amplitude standardization operations are performed, while the other four stages would be the actual differentiators. 

Differentiation would occur by the mechanism of a parallel shunt pathway through slowly-responding inhibitory interneurons, known to be present throughout the hippocampus.

The two long spatial dimensions of the hippocampus would represent frequency and amplitude by setting up gradients in the gain of the differentiators. A given spot in the hippocampal array would map the input function to itself only for one particular combination of frequency and amplitude. 

The self-mapping sets up a positive feedback around the loop that makes the spot stand out functionally. All the concurrently active spots would constitute the context. This context could in principle reach the entire cerebral cortex via the fimbria fornix, mammillary bodies, and tuberomamillary nucleus of the hypothalamus, the latter being histaminergic.

Learning and Novelty 

The cortex may contain a novelty-detection function, source of the well-documented mismatch negativity found in oddball evoked-potential experiments. A stimulus found to be novel would go into a short term memory store in cortex. If a crisis develops while it is there, it is changed into a flash memory and wired up to the amygdala, which mediates visceral fear responses. In this way, a conditioned fear stimulus could be created. If a reward registers while the stimulus is in short term memory, it could be converted to a conditioned appetitive stimulus by a similar mechanism.

It Gets Bigger

I conjecture that all a person's declarative and episodic memories together are nothing more nor less than the context data that were instrumental in conferring conditioned status on particular stimuli.

Context is Required for Novelty

To become such a memory, a stimulus must first be found to be novel, and this is much less likely in the absence of a context signal; to put it another way, it is the combination of the context signal and the sensory stimulus that is found to be novel. Absent the context, and almost no simple stimulus will be novel. This may be the reason why at least one hippocampus must be functioning if declarative or episodic memories are to be formed.

#10. The Two–test-tube Experiment: Part II [neuroscience]

NE

Red, theory; black, fact

This is how the brain would have to work if fragments of skilled behaviors are randomly stored in memory on the left or right side, reflecting the possibility that the two hemispheres play experiment versus control, respectively, during learning.

The Significance of Hemispheric Asymmetry 

The experimenting-brain theory predicts zero hard-wired asymmetries between the hemispheres. However, the accepted theory of hemispheric dominance postulates that this arrangement allows us to do two things at once, one task with the left hemisphere and the other task with the right. The accepted theory is basically a parsimony argument. However, this argument predicts huge differences between the hemispheres, not the subtle ones actually found.

Hard-wired hemispheric dominance may be an imperfection of symmetry in the framework of the experimenting brain caused by the human brain being still in the process of evolving, in light of the hypothesis that brain-expanding mutations individually produce small and asymmetric expansions. Our left-hemispheric speech apparatus is the most asymmetric part of our brain and these ideas predict that we are due for another mutation that will expand the right side, thereby matching up the two sides, resulting in an improvement in the efficiency of operant conditioning of speech behaviour.

These ideas also explain why speech defects such as lisping and stuttering are so common and slow to resolve, even in children, who are supposed to be geniuses at speech acquisition.

Motor Control in an Experimenting Brain

The illustration shows the theory of motor control I was driven to by the implications of the theory of the dichotomously experimenting brain already outlined. It shows how hemispheric dominance can be reversed independently of the side of the body that should perform the movement specified by the applicable rule of conduct in the controlling hemisphere. The triangular device is a summer that converges the motor outputs of both hemispheres into a common output stream that is subsequently gated into the appropriate side of the body. This arrangement cannot create contention because at any given time, only one hemisphere is active. Anatomically, and from stroke studies, it certainly appears that the outputs of the hemispheres must be crossed, with the left hemisphere only controlling the right body and vice-versa.

In healthy individuals, either hemisphere may control either side of the body, and the laterality of control may switch freely and rapidly during skilled performance so as to always use the best rule of conduct at any given time, regardless of the hemisphere in which it was originally created during REM sleep.

Laterality Control Mechanism

The first bit would be calculated and stored in the basal ganglia. It would be output from the reticular substantia nigra (SNr) and gate sensory input to thalamus to favour one hemisphere or the other, by means of actions at the reticular thalamus and intermediate grey of the superior colliculus. The second bit would be stored in the cerebellar hemispheres and gate motor output to one side of the body or the other, at the red nucleus. Conceivably, the two parts of the red nucleus, the parvocellular and the magnocellular, correspond to the adder and switch, respectively, that are shown in the illustration.

Role of the Corpus Callosum

Under these assumptions, the corpus callosum is needed only to distribute priming signals from the motor/premotor cortices to activate the rule that will be next to fire, without regard for which side that rule happens to be on. The callosum would never be required to carry signals forward from sensory to motor areas. I see that as the time-critical step, and it would never depend on getting signals through the corpus callosum, which is considered to be a signaling bottleneck.

Brain Mechanism of Operant Conditioning 

Evaluation 

How would the basal ganglia identify the "best" rule of conduct in a given context? I see the dopaminergic compact substantia nigra (SNc) as the most likely place for a hemisphere-specific "goodness" value to be calculated after each rule firing, using hypothalamic servo-error signals processed through the habenula as the main input for this. The half of the SNc located in the inactive hemisphere would be shut down by inhibitory GABAergic inputs from the adjacent SNr. The dopaminergic nigrostriatal projection would permanently potentiate simultaneously-active corticostriatal inputs (carrying context information) to medium spiny neurons (MSNs) of enkephalin type via a crossed projection, and to MSNs of substance-P type via uncrossed projections. The former MSN type innervates the external globus pallius (GPe), and the latter type innervates the SNr. These latter two nuclei are inhibitory and innervate each other. 

This arrangement sets up a winner-take-all competition between GPe and SNr, with choice of the winner being exquisitely sensitive to small historical differences in dopaminergic tone between hemispheres. The "winner" is the side of the SNr that shuts down sensory input to the hemisphere on that side. The mutually inhibitory arrangement could also plausibly implement hysteresis, which means that once one hemisphere is shut down, it stays shut down without the need for an ongoing signal from the striatum to keep it shut down.

Process Control

Each time the cerebral cortex outputs a motor command, a copy would go to the subthalamic nucleus (STN) and could plausibly serve as the timing signal for a "refresh" of the hemispheric dominance decision based on the latest context information from cortex. The STN signal presumably removes the hysteresis mentioned above, very temporarily, then lets the system settle down again into possibly a new state.

Launching an Experiment 

We now need a system that decides that something is wrong, and that the time to experiment has arrived. This could plausibly be the role of the large, cholinergic interneurons of the striatum. They have a diverse array of inputs that could potentially signal trouble with the status quo, and could implement a decision to experiment simply by reversing the hemispheric dominance prevailing at the time. Presumably, they would do this by a cholinergic action on the surrounding MSNs of both types.

Coding Analogies 

Finally, there is the second main output of the basal ganglia to consider, the inner pallidal segment (GPi). This structure is well developed in primates such as humans but is rudimentary in rodents and even in the cat, a carnivore. It sends its output forward, to motor thalamus. I conjecture that its role is to organize the brain's knowledge base to resemble block-structured programs. All the instructions in a block would be simultaneously primed by this projection. The block identifier may be some hash of the corticostriatal context information. A small group of cells just outside the striatum called the claustrum seems to have the connections necessary for preparing this hash. Jump rules, that is, rules of conduct for jumping between blocks, would not output motor commands, but block identifiers, which would be maintained online by hysteresis effects in the basal ganglia.

The cortical representation of jump rules would likely be located in medial areas, such as Brodmann 23, 24, 31, and 32. Brodmann Areas 23-24 are classed as limbic system, and areas 31-32 are situated between these and neocortex. This arrangement suggests that, seen as a computer, the brain is capable of executing programs with three levels of indentation. Dynamic changes in hemispheric dominance might occur independently in neocortex, medial cortex, and limbic system.