#66. Neuromodulators as Peril Specialists [Neuroscience]

NE

Red: theory; black, fact.

Solanum dulcamara, a plant with anticholinesterase activity.

“Life is Difficulty”

My PhD thesis was about a neuromodulator (acetylcholine) acting on mammalian brain. It was tough to decapitate all those rats; I never got used to it. But if you can’t stand the formaldehyde, get out of the lab.

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.

 

Complications

Glutamate, GABA, and acetylcholine are usually considered neurotransmitters, not neuromodulators, but all three have G-protein-coupled receptors in addition to ionotropic receptors and are thus both.

In thermoregulation, hypothalamic glutamate and GABA act on the body via the serotonergic raphe pallidus nucleus. The implied connection with predation (See table) would be due to the fact that animals become torpid at extremes of temperature and thus easy prey. The larger predator would have a smaller surface to volume ratio and thus slower warming and cooling after leaving its refugium to hunt. The predator thermal advantage would have been the selection pressure for thermal sensitivity in the anti-predation system, which eventually became upstream of temperature regulation effectors generally. 

The functional assignments suggested in Table 1 would mostly pertain to a very primordial brain. The implication is that any modern biological function of the neuromodulator substance other than organizing the response to a specific type of peril was elaborated out of the primordial function over long-term evolution, which can act opportunistically to confer new functions on preexisting adaptations.

An example of such elaboration is shown for dopamine in the inferred social role. A pre-adaptation for this role split may have been breast-feeding.

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

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

PO     EN     EP     NE     GE     

Red, theory; black, fact.

6-01-2018; 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. From several lines of evidence, I keep coming back to the idea that humans must 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.

I here propose that the natural population curve for humans in good times is 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 to which I allude many times in these pages. 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 by instinctive factors, but not to a constant absolute density, but rather 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.

My formal training in engineering and neuroscience justifies a bit of speculation as to mechanisms at this point. Look first for such a controller in the hypothalamus, already known to control other variables, such as temperature, by feedback principles.

In school, I was taught that nature does not reinvent the wheel, 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.

I will continue to assume that the controller is a conventional PID controller, as in previous posts. To make it control rate of increase rather than absolute population density, you put a differentiator in the feedback pathway. Look first in the amygdala for such a differentiator. 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. 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 just inhibit the feed-forward pathway pharmacologically as specifically as may be, 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.

I assumed in the last post that the political convulsions that produce dispersal are triggered by the value on the integrator of the PID controller rising above a threshold. However, in the above design solution, the convulsion would be triggered by the raw, undifferentiated population-density signal rising above some threshold. Look in the amygdala for this signal as well. Consistent with this, bilateral removal of the amygdalae and hippocampi in monkeys is known to have a profound taming effect accompanied by hypersexuality, known as the Kluver-Bucy syndrome.

6-17-2018: To be consistent, I would have to say that the differentiator for the population signal is more likely to be in the hippocampal formation by the argument of nature not reinventing the wheel, because in an earlier post, I interpreted the hippocampus as the site of four successive differentiations that carry out a Fourier transform by mapping sinusiodal waves back onto themselves at a particular best frequency, in the presence of a map of such best frequencies.

However, this setup would require the creation of two neuron-to-neuron connections for its evolution; a first connection to send the amygdalar raw population signal to the hippocampus, and a second to send the differentiated result back for further processing. At best, this would require two simultaneous mutations. Either change by itself would be at best useless and could never be selected. This appears to be another example of irreducible complexity requiring the bi-mutation mechanism described in the previous post. 

The mechanisms usually offered to explain cases of apparent irreducible complexity, such as spandrelling, exaptation, and scaffolding, all appear to lack time efficiency and processiveness. I previously said that in evolution there are no (absolute)  deadlines, but relative deadlines can easily be created by an interaction of processes. In the presence of relative deadlines, such as adaptive footraces to be the first clade to exploit a newly-habitable area or a new niche, time is of the essence and selection for speed and evolvability can be expected. Such selection will create mechanisms such as crossing over that enhance evolvability.

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

EP    NE    GE

Red, theory; black, fact.

12-17-2017: In previous posts, I theorized that humans, along with all other sexually-reproducing species, have a long-range guidance system that I called proxy natural selection, or preferably, post-zygotic gamete selection (PGS), that is basically a fast form of evolution in which individual 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.

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.

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 are theorized to 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, I believe you have all the essential ingredients of classical natural selection, and all the potential, in a process that solves problems on an historical timescale.

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.

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. Check this out in the literature, and you will already find a strange diversity of cell-surface receptors on the spermatogonia. (I haven't looked at oogonia yet.&&) 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 behavioral traits, not their averages.

1-09-2018: 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. Exactly five second-messenger systems are known, these being based on: cyclic AMP, inositol triphosphate, cyclic GMP, arachidonic acid, and small GTPases (e.g., ras). However, many mammalian species have many more than the 32 chromosome pairs needed to saturate a 5-bit address space.

1-10-2018: 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.

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.

Each pair of homologous chromosomes may correspond to what in an earlier post was called a "PNS focus." 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.

A related concept is that a chromosome specifies an ancestral, generic cell type, like glial cells (4 subtypes known) or muscle cells (3 subtypes known). The great diversity of the neurons suggest that they must be reclassified into multiple basic types, perhaps along the lines suggested by the functional classification of the cranial nerves: general somatic, general visceral, and special somatic (i.e., specific senses).

1-09-2018: A third concept for function assignment to homologous pairs of chromosomes postulates a hypothetical maximally divided genome in which each cell type has its own chromosome pair, a state conjectured to seldom occur in nature. Co-evolution of clusters of cell types (e.g., neurons and glia; bone and cartilage) would create selection pressure for the underlying cell-type-specific chromosomes to become covalently linked into the larger chromosomes that we see in the actual karyotypes. Thus, each observed homologous pair would correspond to a few cell types that are currently co-evolving, which seems to return us to the system or organ concept. 

01-08-2019: The system specified by a chromosome may be called a cooperation system, and these may be organized in a hierarchy, following the general principles of spatial organization outlined in my post: "The Pictures in Your Head." Chromosomes activated earlier in development will specify system-like entities and those activated late in development will specify organ-like entities. Only the first-activated chromosome will apply to the entire organism.

Humans depend on complex social structures for their survival, and this comes out of our individual behavioral tendencies. Probably, most PGS adaptations to environmental fluctuations involve modifying these structures, which would come out of subtle modifications of individual behaviors. I think I am just repeating E.O. Wilson here. Our hard-wired species-fitness definitions would give rise to the primary emotions, perhaps in the hypothalamus or limbic system, by connecting specific stimuli to primary emotions in the manner of an if-then rule. 

Further out on the cortex, the specific stimuli being connected would get progressively more complex and learning-dependent, and progressively less concerned with the "what" of behavior (i.e., our species-specific taxes) and more with the "how" of behavior. In "how" mode, the complex stimuli become more like signposts to be consulted on a journey. PGS adaptations of our behavior would affect the hardwired aspects of this hypothetical transition zone. The primary emotions would then be like the highest hierarchical level of our motor program, or like the least-indented instructions of a conventional high-level computer program.

I conjecture that religion is important because it goes straight for this highest level. We all know that religion is kind of an emotional business, what with the organ music and the stained glass and all such as that, and this is why. I therefore conjecture that words spoken often from the pulpit, such as God, sin, forgiveness, devil, angel, soul, salvation, etc., all enclose a secret that writers such as Dawkins do not grasp: the emotions are the message. To illustrate this, let us attempt an emotional definition of the master symbol, "God."

God: feeling loved and secure to the point of invulnerability; feeling small in an agreeable way, as in the presence of mountains; feeling brotherly/sisterly towards one's fellow humans; blossoming in confidence into one's full potential; fearing nothing.

Perhaps that's enough to give the general idea. No doubt a whole dictionary could be compiled along these lines. When the priest strings these emotion-words together, he creates an experience for the congregation that could fairly be called a form letter from "God," assuming that the word "God" points to the PGS process itself. The job of the priest is to help the congregation relate on a deep level to the sacred texts and to see/feel how they apply to the challenges of the here and now.

7-05-2018: Another term for PGS would be "Yahwetion," from "Yahweh," the conventional modern spelling of the name of the god of ancient Israel, and the "tion" ending indicating a process, like evolution. This neologism advantageously steers people away from category errors like attempting to worship it, or appease it, or what have you.

The conventionally religious will complain that this would make prayer to God impossible, but not if prayer itself is re conceived as "auto socialization," following the educational theory of prayer. Then prayer becomes a fantasy conversation with anyone, living or dead, that you would like to have as a mentor, if it were possible.

#28. The Origin of Consciousness [neuroscience]

NE

Red, theory; black, fact.

After perusing Gideon Rosenblatt's blog at the prompting of Google, I finally saw the need for this post.

I theorize that 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 bulk on one side of a fractal line and sensory data the bulk 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.

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

EP

Red, theory; black, fact.

My last post about proxy natural selection (PNS) has directed me to emphasize emotion more in seeking explanations for human behavior. I now think of emotions as an "endophenotype," to use a term from functional magnetic resonance imaging, that provides a useful stepping stone from evolutionary arguments to explanations of our daily lives. I recently applied this insight to obtaining a second explanation of religion, alternative or parallel to the first one that I give in a previous post.

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." However, I want to translate that statement into a sociobiological function assignment. My discussion "Proxy Natural Selection from the Inside" suggests a problem: if the emotional outlines of people's behavior 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 everyones' betes noir. The purpose of a king may be to find or at least 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. 

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. 

Kingship comes the corrupting influence of personal power, leading to destructive, tyrannical governments. 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 all flexibility, the flexibility that goes with having a flesh-and-blood king who can change his predecessor's laws based on current popular sentiment.

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 previously alluded to in post #16, and produced by species-replacement group selection within the genus, and the latter would be due to PNS, 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 unchanging, could be taught 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 (not part of PNS), necessitating the standardizing role of religion. Synaptic plasticity would then be used to cancel the point-mutational variation in the objective function.

This core  consists of four pillars, or themes: genetic diversity, memetic diversity, altruism, and dispersal. Our energetic investment in obtaining each item is to be optimized. To produce this, the church of my acquaintance is continually emphasizing, respectively, tolerance, creating beautiful things, charity, and justice. It's almost too neat, especially if we adopt the deeply cynical-sounding position that the demand for "justice" only polarizes groups to the point of schism and diaspora.

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

EP    GE    

Red, theory; black, fact.

My first post on proxy natural selection (PNS) 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.

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. I also think that each activation of an emotion tends 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.

To relate this to the mechanism of PNS, the crossing-over events that went into making the sperm cell that made you would theoretically affect brain development more than anything else, specifically connecting some random stimulus to one of the unpleasant primary emotions. This creates your temperament, and thus your personality, which is the unique quality which you have to offer the world, and on which you are being tested by history. If the actions to which your own, special bete noir propel you are what the species objective function is looking for, you succeed, feel joy and serenity, and experience an altered methylation status of the DNA in your spermatogonia, if you are male, which (I conjecture) suppresses further crossing over in the manufacture of your own sperm, so that your personality type breeds true, which is what the population needs. 

PNS is quickie evolution to respond to challenges that come and go on less than a multi-thousand generation timescale, and I conjecture that it explains the complexities of sexual reproduction. You may object that trees, for example, 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.

Here is my own self-analysis in terms of PNS theory. My special emotional novelty that is potentially my gift to the world is a morbid fear of social rejection. This has motivated much more than the usual self-criticism of my own creative productions before they are communicated to others, for fear of rejection, leading to the kind of thing you are now reading. Social rejection/criticism hits me like a wall of flame that burns for days, or like some kind of rays coming out of the other person's head. The rejection that goes with the dating game has made it intolerable to me, leading to a lifelong celibacy that has freed all my resources for scientific pursuits. 

My father was a general in the Canadian Armed Forces, and was most unlike this, but my older brother takes after him somewhat. What happened to sour my father's life so radically before my birth in 1953, so that his recombinotype (coined word) no longer bred true? I conjecture that it was the failure of the defeat of Nazi Germany to produce a true, lasting peace, only ushering in the nuclear cold war with the USSR. With this, "God" was telling us: "Don't study war no more."

Each of the four unpleasant "starting" emotions may sub serve one of the four pillars of the species objective function already listed in The intermind: Engine of History?. Thus: sadness, altruism; disgust, genetic diversity (due to point mutations; what is motivated here is the screening of such novelties, screening always being the expensive part); fear, memetic diversity (or motivating prescreening of memetic novelties); 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. 

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

EV    GE    

Red, theory; black, fact.

2-06-2017

As promised, here is my detailed and hypothetical description of the entity 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, "proxy natural selection" (PNS) is DNA-based.

11-20-2017

The acronym PNS is liable to be confused with "peripheral nervous system," so a better acronym would be "PGS," meaning "post-zygotic gamete selection."

2-06-2017

First, a refresher on how standard natural selection works. DNA undergoes point mutations (I will deal with the other main type of mutation later) 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.

PNS 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.

Here is how PNS may work. 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 oligogenerational timescale. On such a timescale, neither standard natural selection nor synapse-based learning systems are serviceable.

2-07-2017

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 PNS.

7-29-2017

Here is a better theory of female PNS. First, we need a definition. PNS focus: a function that is the target of most PNS. Thus, in trees, the PNS focus is bio elaboration of natural pesticides. In human males, the PNS focus is brain development and the broad outlines of emotional reactivity, and thus behavior. In human females, the PNS focus is 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.

8-18-2017

Experimental evidence for my proposed recombination mechanism of proxy natural selection 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

permalink:

http://ncsu.summon.serialssolutions.com/#!/search?bookMark=ePnHCXMwfV1NS8QwEC2yBz9-gxL0JgTytUl7EUQU767nkDQJeCgu7uLv903SVlEQepx0pmky8yaTvJx3G-StuZsLiKLydSpLO8QEx8Ry3J3QgR9Nmx6t2tAivxGcaNhOFw9qZd-fdXcv9bQER26Kr0yMMsQJ6WK1mCHPZoBIbMp0QvbtMLH3wjKm9GfjtwbEen163D088_lSAT4i9js-xgi_DdSQBplcwQhXIQSggNjHVEpwUlIlK-uSyJI4JMRspZKKymyzTfqiu27vXVy3n__6wQO9GARIQVXsqyZEbt7TWDl-hNEj1wHg2A5EOiqbwBIM_b6xS_iVR7h2mxcNpTtPN7vf_NIcIq2HjEeotopifT_8L_XDwNsmtZR_V_2ECDxpxqOr6m9j_wpDiOrp_r6N82bqPhW0uWxt6i7PtYGRhgh9lP4C2uagLw

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 signaling pathways, itself  evolves, by species-replacement group selection. Support for that idea is the next thing I must search for in the literature. &&

#22. The Cogs of Armageddon [evolutionary psychology]

EP

Red, theory; black, fact.

1-27-2017

This is a "just-so story" about how I believe everyday human behavior eventually accomplishes the all-important biological function of dispersal for the human race. A future post will attempt to explain how the "just-so story" got written in terms of natural selection and possible faster-acting proxies thereof needed by organisms with long generation times.

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. To paraphrase the latter, a way to avoid extinction, long-term, is not putting all your eggs in one basket, geographically speaking.

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.

I conjecture that human neural pathways potentiate aggression when the hard times come, but of an elaborate kind adapted for ensuring efficient dispersal (i.e., with minimal loss of life). It begins with a two-person feud of the sort illustrated in cultural references too numerous to mention. In Canada, where I live, a cough accompanied by an angry expression plays the role of the instigation. The arbitrary stimulus, made offensive by some piece of Pavlovian conditioning, is traded back and forth with rapidly increasing energy. The process is remarkably like flirting, not surprising since the ultimate purpose has commonalities with reproduction--but of an entire society. 

However, the emotional component is strongly threatening rather than rewarding, 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.

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. 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 dearly like to do to the other by this point. This, again, is an efficiency from the point of view of producing dispersal.

However, if each side is continually threatening the other, why don't they flee each other's presence during the very early stages? The answer seems to be that humans have a reflex that converts feeling threatened into a wish to injure the threatening party, possibly a behavioral leftover from some earlier adaptation, such as an anti-predation defense; to injure, you have to stick around. (Leftovers such as these form the building blocks of future just-so plots.)

Finally, settled refugees usually do not integrate completely into the host society, instead forming ethnic neighborhoods. This increases the resemblance to an entire society reproducing itself. However, the growth phase following reproduction in individuals seems to be lacking at the society level. However, being seen as ethnic by the host society, due to slow integration, could improve individual-level reproductive success of refugees because of disassortative mate-choice effects evolved to favor genes that produce dispersal.

2-24-2017

The dispersal-producing dynamic just outlined is fantastically powerful, as it must be to overcome all the reasons you would not leave your 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., etc.

This dynamic is basically what theologians call evil, for which I propose the less judgmental, substitute term "dispersalism." If this is truly an insight, it should have a liberating effect on your life, even if you just remember that one word, but with the price of always being population-conscious: always trying to see what is happening at the population/zeitgeist level, and reading the paper every day at the very least.

At least one "just-so story" could probably be written for each of the pillars of the human species-specific objective function mentioned in previous posts, these being as follows: dispersal, genetic diversity, memetic diversity, and altruism. (The latter has not been mentioned until now.) Each of these must be optimized, not blindly maximized, for each comes at a cost. In terms of neurobiology, each pillar is probably a family of functionally related likes and dislikes wired up in the hypothalamus, but not obviously related to individual-level survival or reproduction.

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

EN    NE    

Red, theory; black, fact.

"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?

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

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. 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. 

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. 

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 to hippocampal CA3 to hippocampal CA1 to subiculum to entorhinal cortex, 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 other two 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 array maps the input function to itself only for one particular combination of frequency and transformed (i.e., output) amplitude. 

The self-mapping sets up a reverberation 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.

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.

 I conjecture that all a person's declarative and episodic memories together are nothing more nor less than those that confer conditioned status on particular stimuli.

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.

At this point we have a problem. 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.

My solution is that hard-wired hemispheric dominance must be seen as an imperfection of symmetry in the framework of the experimenting brain caused by the human brain being still in the process of evolving, combined with the hypothesis that brain-expanding mutations individually produce small and asymmetric expansions. (See Post 45.) 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 behavior.

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.

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 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.

However, my theory predicts that in healthy individuals, either hemisphere can control either side of the body, and the laterality of control can 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.

The first bit is calculated and stored in the basal ganglia. It would be output from the reticular substantia nigra (SNr) and gate sensory input to thalamus to favor 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.

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.

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. 

I conjecture that this arrangement sets up a winner-take-all kind of 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.

Each time the cerebral cortex outputs a motor command, a copy goes 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.

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 inter neurons 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.

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. BA23-24 is classed as limbic system, and BA31-32 is situated between this and neocortex. This arrangement suggests that, seen as a computer, the brain is capable of executing programs with three levels of indentation, not counting whatever levels may be encoded as chromatin marks in the serotonergic neurons. Dynamic changes in hemispheric dominance might have to occur independently in neocortex, medial cortex, and limbic system.